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<div class="mw-indicators"> </div> <div id="siteSub" class="noprint">From Wikipedia, the free encyclopedia</div> </div> <div id="contentSub"><div id="mw-content-subtitle"></div></div> <div id="mw-content-text" class="mw-body-content"><div class="mw-content-ltr mw-parser-output" lang="en" dir="ltr"><div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">Intracellular communication process</div> <figure typeof="mw:File/Thumb"><a href="/wiki/File:Calcium_Signaling_Pathway.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/0/0e/Calcium_Signaling_Pathway.png/305px-Calcium_Signaling_Pathway.png" decoding="async" width="305" height="181" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/0/0e/Calcium_Signaling_Pathway.png/458px-Calcium_Signaling_Pathway.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/0/0e/Calcium_Signaling_Pathway.png/610px-Calcium_Signaling_Pathway.png 2x" data-file-width="1526" data-file-height="907" /></a><figcaption>Shows Ca<sup>2+</sup> release from the <a href="/wiki/Endoplasmic_reticulum" title="Endoplasmic reticulum">endoplasmic reticulum</a> through <a href="/wiki/Phospholipase_C" title="Phospholipase C">phospholipase C (PLC)</a> pathway.</figcaption></figure> <p><b>Calcium signaling</b> is the use of <a href="/wiki/Calcium_in_biology" title="Calcium in biology">calcium ions</a> (Ca<sup>2+</sup>) to communicate and drive intracellular processes often as a step in <a href="/wiki/Signal_transduction" title="Signal transduction">signal transduction</a>. Ca<sup>2+</sup> is important for <a href="/wiki/Cell_signaling" title="Cell signaling">cellular signalling</a>, for once it enters the <a href="/wiki/Cytosol" title="Cytosol">cytosol</a> of the <a href="/wiki/Cytoplasm" title="Cytoplasm">cytoplasm</a> it exerts <a href="/wiki/Allosteric" class="mw-redirect" title="Allosteric">allosteric</a> regulatory effects on many <a href="/wiki/Enzyme" title="Enzyme">enzymes</a> and <a href="/wiki/Protein" title="Protein">proteins</a>. Ca<sup>2+</sup> can act in signal transduction resulting from activation of <a href="/wiki/Ion_channels" class="mw-redirect" title="Ion channels">ion channels</a> or as a <a href="/wiki/Second_messenger_system" title="Second messenger system">second messenger</a> caused by indirect signal transduction pathways such as <a href="/wiki/G_protein-coupled_receptors" class="mw-redirect" title="G protein-coupled receptors">G protein-coupled receptors</a>. </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="Concentration_regulation">Concentration regulation</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Calcium_signaling&action=edit&section=1" title="Edit section: Concentration regulation"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The resting concentration of Ca<sup>2+</sup> in the <a href="/wiki/Cytoplasm" title="Cytoplasm">cytoplasm</a> is normally maintained around 100 <a href="/wiki/Molar_concentration" title="Molar concentration">nM</a>. This is 20,000- to 100,000-fold lower than typical extracellular concentration.<sup id="cite_ref-pmid18083096_1-0" class="reference"><a href="#cite_note-pmid18083096-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Demaurex_2016_2-0" class="reference"><a href="#cite_note-Demaurex_2016-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> To maintain this low concentration, Ca<sup>2+</sup> is actively pumped from the cytosol to the extracellular space, the <a href="/wiki/Endoplasmic_reticulum" title="Endoplasmic reticulum">endoplasmic reticulum</a> (ER), and sometimes into the <a href="/wiki/Mitochondria" class="mw-redirect" title="Mitochondria">mitochondria</a>. Certain proteins of the cytoplasm and <a href="/wiki/Organelle" title="Organelle">organelles</a> act as buffers by binding Ca<sup>2+</sup>. Signaling occurs when the cell is stimulated to release Ca<sup>2+</sup> ions from intracellular stores, and/or when Ca<sup>2+</sup> enters the cell through <a href="/wiki/Cell_membrane" title="Cell membrane">plasma membrane</a> ion channels.<sup id="cite_ref-pmid18083096_1-1" class="reference"><a href="#cite_note-pmid18083096-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> Under certain conditions, the intracellular Ca<sup>2+</sup> concentration may begin to oscillate at a specific frequency.<sup id="cite_ref-pmid10864327_3-0" class="reference"><a href="#cite_note-pmid10864327-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Phospholipase_C_pathway">Phospholipase C pathway</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Calcium_signaling&action=edit&section=2" title="Edit section: Phospholipase C pathway"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure typeof="mw:File/Thumb"><a href="/wiki/File:PLC_role_in_IP3-DAG_pathway.tif" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/7/76/PLC_role_in_IP3-DAG_pathway.tif/lossy-page1-287px-PLC_role_in_IP3-DAG_pathway.tif.jpg" decoding="async" width="287" height="115" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/7/76/PLC_role_in_IP3-DAG_pathway.tif/lossy-page1-431px-PLC_role_in_IP3-DAG_pathway.tif.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/7/76/PLC_role_in_IP3-DAG_pathway.tif/lossy-page1-574px-PLC_role_in_IP3-DAG_pathway.tif.jpg 2x" data-file-width="717" data-file-height="287" /></a><figcaption>Phospholipase C cleaving PIP2 into IP3 and DAG</figcaption></figure> <p>Specific signals can trigger a sudden increase in the cytoplasmic Ca<sup>2+</sup> levels to 500–1,000 nM by opening channels in the ER or the <a href="/wiki/Plasma_membrane" class="mw-redirect" title="Plasma membrane">plasma membrane</a>. The most common signaling pathway that increases cytoplasmic calcium concentration is the <a href="/wiki/Phospholipase_C" title="Phospholipase C">phospholipase C (PLC)</a> pathway. </p> <ol><li>Many <a href="/wiki/Cell_surface_receptor" title="Cell surface receptor">cell surface receptors</a>, including <a href="/wiki/G_protein-coupled_receptors" class="mw-redirect" title="G protein-coupled receptors">G protein-coupled receptors</a> and <a href="/wiki/Receptor_tyrosine_kinase" title="Receptor tyrosine kinase">receptor tyrosine kinases</a>, activate the PLC enzyme.</li> <li>PLC uses <a href="/wiki/Hydrolysis" title="Hydrolysis">hydrolysis</a> of the membrane phospholipid <a href="/wiki/PIP2" class="mw-redirect" title="PIP2">PIP<sub>2</sub></a> to form <a href="/wiki/Inositol_trisphosphate" title="Inositol trisphosphate">IP<sub>3</sub></a> and <a href="/wiki/Diacylglycerol" class="mw-redirect" title="Diacylglycerol">diacylglycerol</a> (DAG), two classic secondary messengers.</li> <li>DAG attaches to the plasma membrane and recruits <a href="/wiki/Protein_kinase_C" title="Protein kinase C">protein kinase C</a> (PKC).</li> <li>IP<sub>3</sub> diffuses to the ER and is bound to the <a href="/wiki/IP3_receptor" class="mw-redirect" title="IP3 receptor">IP3 receptor</a>.</li> <li>The IP<sub>3</sub> receptor serves as a Ca<sup>2+</sup> channel, and releases Ca<sup>2+</sup> from the ER.</li> <li>The Ca<sup>2+</sup> bind to PKC and other proteins and activate them.<sup id="cite_ref-4" class="reference"><a href="#cite_note-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup></li></ol> <div class="mw-heading mw-heading3"><h3 id="Depletion_from_the_endoplasmic_reticulum">Depletion from the endoplasmic reticulum</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Calcium_signaling&action=edit&section=3" title="Edit section: Depletion from the endoplasmic reticulum"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Depletion of Ca<sup>2+</sup> from the ER will lead to Ca<sup>2+</sup> entry from outside the cell by activation of "Store-Operated Channels" (<a href="/wiki/SOC_channels" title="SOC channels">SOCs</a>).<sup id="cite_ref-5" class="reference"><a href="#cite_note-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> This inflow of Ca<sup>2+</sup> is referred to as Ca<sup>2+</sup>-release-activated Ca<sup>2+</sup> current (<a href="/wiki/Calcium_release_activated_channel" title="Calcium release activated channel">ICRAC</a>). The mechanisms through which ICRAC occurs are currently still under investigation. Although Orai1 and <a href="/wiki/STIM1" title="STIM1">STIM1</a>, have been linked by several studies, for a proposed model of store-operated calcium influx. Recent studies have cited the <a href="/wiki/Phospholipase" title="Phospholipase">phospholipase</a> A2 beta,<sup id="cite_ref-6" class="reference"><a href="#cite_note-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Nicotinic_acid_adenine_dinucleotide_phosphate" title="Nicotinic acid adenine dinucleotide phosphate">nicotinic acid adenine dinucleotide phosphate</a> (NAADP),<sup id="cite_ref-7" class="reference"><a href="#cite_note-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> and the protein <a href="/wiki/STIM1" title="STIM1">STIM 1</a><sup id="cite_ref-8" class="reference"><a href="#cite_note-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> as possible mediators of ICRAC. </p> <div class="mw-heading mw-heading2"><h2 id="As_a_second_messenger">As a second messenger</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Calcium_signaling&action=edit&section=4" title="Edit section: As a second messenger"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Calcium is a ubiquitous <a href="/wiki/Second_messenger_system" title="Second messenger system">second messenger</a> with wide-ranging physiological roles.<sup id="cite_ref-Demaurex_2016_2-1" class="reference"><a href="#cite_note-Demaurex_2016-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> These include <a href="/wiki/Muscle_contraction" title="Muscle contraction">muscle contraction</a>, neuronal transmission (as in an <a href="/wiki/Excitatory_synapse" title="Excitatory synapse">excitatory synapse</a>), cellular <a href="/wiki/Motility" title="Motility">motility</a> (including the movement of <a href="/wiki/Flagella" class="mw-redirect" title="Flagella">flagella</a> and <a href="/wiki/Cilia" class="mw-redirect" title="Cilia">cilia</a>), <a href="/wiki/Fertilisation" title="Fertilisation">fertilization</a>, <a href="/wiki/Cell_growth" title="Cell growth">cell growth</a> (proliferation), <a href="/wiki/Neurogenesis" title="Neurogenesis">neurogenesis</a>, learning and memory as with <a href="/wiki/Synaptic_plasticity" title="Synaptic plasticity">synaptic plasticity</a>, and secretion of <a href="/wiki/Saliva" title="Saliva">saliva</a>.<sup id="cite_ref-9" class="reference"><a href="#cite_note-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-10" class="reference"><a href="#cite_note-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> High levels of cytoplasmic Ca<sup>2+</sup> can also cause the cell to undergo <a href="/wiki/Apoptosis" title="Apoptosis">apoptosis</a>.<sup id="cite_ref-11" class="reference"><a href="#cite_note-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> Other biochemical roles of calcium include regulating <a href="/wiki/Enzyme" title="Enzyme">enzyme</a> activity, permeability of <a href="/wiki/Ion_channels" class="mw-redirect" title="Ion channels">ion channels</a>,<sup id="cite_ref-12" class="reference"><a href="#cite_note-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> activity of <a href="/wiki/Ion_pump_(biology)" class="mw-redirect" title="Ion pump (biology)">ion pumps</a>, and components of the <a href="/wiki/Cytoskeleton" title="Cytoskeleton">cytoskeleton</a>.<sup id="cite_ref-13" class="reference"><a href="#cite_note-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> </p><p>Many of Ca<sup>2+</sup> mediated events occur when the released Ca<sup>2+</sup> binds to and activates the regulatory protein <a href="/wiki/Calmodulin" title="Calmodulin">calmodulin</a>. Calmodulin may activate the Ca<sup>2+</sup>-calmodulin-dependent <a href="/wiki/Protein_kinase" title="Protein kinase">protein kinases</a>, or may act directly on other effector proteins.<sup id="cite_ref-14" class="reference"><a href="#cite_note-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> Besides calmodulin, there are many other Ca<sup>2+</sup>-binding proteins that mediate the biological effects of Ca<sup>2+</sup>. </p> <div class="mw-heading mw-heading3"><h3 id="In_muscle_contractions">In muscle contractions</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Calcium_signaling&action=edit&section=5" title="Edit section: In muscle contractions"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure typeof="mw:File/Thumb"><a href="/wiki/File:Comparison_of_smooth_muscle_and_skeletal_muscle_contraction.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/4/46/Comparison_of_smooth_muscle_and_skeletal_muscle_contraction.png/342px-Comparison_of_smooth_muscle_and_skeletal_muscle_contraction.png" decoding="async" width="342" height="257" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/4/46/Comparison_of_smooth_muscle_and_skeletal_muscle_contraction.png/513px-Comparison_of_smooth_muscle_and_skeletal_muscle_contraction.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/4/46/Comparison_of_smooth_muscle_and_skeletal_muscle_contraction.png/684px-Comparison_of_smooth_muscle_and_skeletal_muscle_contraction.png 2x" data-file-width="960" data-file-height="720" /></a><figcaption>Comparison of smooth muscle and skeletal muscle contraction</figcaption></figure> <p>Contractions of skeletal <a href="/wiki/Skeletal_muscle" title="Skeletal muscle">muscle fiber</a> are caused due to electrical stimulation. This process is caused by the <a href="/wiki/Depolarization" title="Depolarization">depolarization</a> of the <a href="/wiki/T-tubule" title="T-tubule">transverse tubular junctions</a>. Once depolarized the <a href="/wiki/Sarcoplasmic_reticulum" title="Sarcoplasmic reticulum">sarcoplasmic reticulum (SR)</a> releases Ca<sup>2+</sup> into the myoplasm where it will bind to a number of calcium sensitive buffers. The Ca<sup>2+</sup> in the myoplasm will diffuse to Ca<sup>2+</sup> regulator sites on the <a href="/wiki/Actin" title="Actin">thin filaments</a>. This leads to the actual contraction of the muscle.<sup id="cite_ref-15" class="reference"><a href="#cite_note-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup> </p><p>Contractions of smooth muscle fiber are dependent on how a Ca<sup>2+</sup> influx occurs. When a Ca<sup>2+</sup> influx occurs, <a href="/wiki/Sliding_filament_theory" title="Sliding filament theory">cross bridges</a> form between <a href="/wiki/Myosin" title="Myosin">myosin</a> and <a href="/wiki/Actin" title="Actin">actin</a> leading to the contraction of the muscle fibers. Influxes may occur from extracellular Ca<sup>2+</sup> diffusion via ion channels. This can lead to three different results. The first is a uniform increase in the Ca<sup>2+</sup> concentration throughout the cell. This is responsible for increases in vascular diameters. The second is a rapid time dependent change in the membrane potential which leads to a very quick and uniform increase of Ca<sup>2+</sup>. This can cause a spontaneous release of <a href="/wiki/Neurotransmitter" title="Neurotransmitter">neurotransmitters</a> via <a href="/wiki/Sympathetic_nervous_system" title="Sympathetic nervous system">sympathetic</a> or <a href="/wiki/Parasympathetic_nervous_system" title="Parasympathetic nervous system">parasympathetic</a> nerve channels. The last potential result is a specific and localized subplasmalemmal Ca<sup>2+</sup> release. This type of release increases the activation of <a href="/wiki/Protein_kinase" title="Protein kinase">protein kinase</a>, and is seen in <a href="/wiki/Cardiac_muscle" title="Cardiac muscle">cardiac muscle</a> where it causes excitation-concentration coupling. Ca<sup>2+</sup> may also result from internal stores found in the SR. This release may be caused by <a href="/wiki/Ryanodine_receptor" title="Ryanodine receptor">Ryaodine (RYRs)</a> or IP<sub>3</sub> receptors. RYRs Ca<sup>2+</sup> release is spontaneous and localized. This has been observed in a number of smooth muscle tissues including <a href="/wiki/Artery" title="Artery">arteries</a>, <a href="/wiki/Portal_vein" title="Portal vein">portal vein</a>, <a href="/wiki/Urinary_bladder" class="mw-redirect" title="Urinary bladder">urinary bladder</a>, <a href="/wiki/Ureter" title="Ureter">ureter</a> tissues, <a href="/wiki/Airway" class="mw-redirect" title="Airway">airway tissues</a>, and <a href="/wiki/Gastrointestinal_tract" title="Gastrointestinal tract">gastrointestinal</a> tissues. IP<sub>3</sub> Ca<sup>2+</sup> release is caused by activation of the IP<sub>3</sub> receptor on the SR. These influxes are often spontaneous and localized as seen in the <a href="/wiki/Colon_(organ)" class="mw-redirect" title="Colon (organ)">colon</a> and portal vein, but may lead to a global Ca<sup>2+</sup> wave as observed in many vascular tissues.<sup id="cite_ref-16" class="reference"><a href="#cite_note-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="In_neurons">In neurons</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Calcium_signaling&action=edit&section=6" title="Edit section: In neurons"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In <a href="/wiki/Neuron" title="Neuron">neurons</a>, concomitant increases in cytosolic and mitochondrial Ca<sup>2+</sup> are important for the synchronization of neuronal electrical activity with mitochondrial energy metabolism. <a href="/wiki/Mitochondrial_matrix" title="Mitochondrial matrix">Mitochondrial matrix</a> Ca<sup>2+</sup> levels can reach the tens of <a href="/wiki/Molar_concentration" title="Molar concentration">μM</a> levels that are necessary for the activation of <a href="/wiki/Isocitrate_dehydrogenase" title="Isocitrate dehydrogenase">isocitrate dehydrogenase</a>, which is one of the key regulatory enzymes of the <a href="/wiki/Krebs_cycle" class="mw-redirect" title="Krebs cycle">Krebs cycle</a>.<sup id="cite_ref-17" class="reference"><a href="#cite_note-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-18" class="reference"><a href="#cite_note-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> </p><p>The ER, in neurons, may serve in a network integrating numerous extracellular and intracellular signals in a binary membrane system with the plasma membrane. Such an association with the plasma membrane creates the relatively new perception of the ER and theme of "a neuron within a neuron." The ER's structural characteristics, ability to act as a Ca<sup>2+</sup> sink, and specific Ca<sup>2+</sup> releasing proteins, serve to create a system that may produce regenerative waves of Ca<sup>2+</sup> release. These may communicate both locally and globally in the cell. These Ca<sup>2+</sup> signals integrate extracellular and intracellular fluxes, and have been implicated to play roles in synaptic plasticity, memory, <a href="/wiki/Neurotransmitter" title="Neurotransmitter">neurotransmitter</a> release, neuronal excitability, and long term changes at the gene transcription level. ER stress is also related to Ca<sup>2+</sup> signaling and along with the unfolded protein response, can cause ER associated degradation (ERAD) and autophagy.<sup id="cite_ref-19" class="reference"><a href="#cite_note-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> </p><p>Astrocytes have a direct relationship with neurons through them releasing gliotransmitters. These transmitters allow communication between neurons and are triggered by calcium levels increasing around astrocytes from inside stores. This increase in calcium can also be caused by other neurotransmitters. Some examples of gliotransmitters are ATP and glutamate. <sup id="cite_ref-20" class="reference"><a href="#cite_note-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> Activation of these neurons will lead to an increase in the concentration of calcium in the cytosol from 100 nanomolar to 1 micromolar.<sup id="cite_ref-21" class="reference"><a href="#cite_note-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="In_fertilization">In fertilization</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Calcium_signaling&action=edit&section=7" title="Edit section: In fertilization"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Ca<sup>2+</sup> influx during fertilization has been observed in many species as a trigger for development of the <a href="/wiki/Oocyte" title="Oocyte">oocyte</a>. These influxes may occur as a single increase in concentration as seen with fish and <a href="/wiki/Echinoderm" title="Echinoderm">echinoderms</a>, or may occur with the concentrations <a href="/wiki/Oscillation" title="Oscillation">oscillating</a> as observed in <a href="/wiki/Mammal" title="Mammal">mammals</a>. The triggers to these Ca<sup>2+</sup> influxes may differ. The influx have been observed to occur via membrane Ca<sup>2+</sup> conduits and Ca<sup>2+</sup> stores in the <a href="/wiki/Sperm" title="Sperm">sperm</a>. It has also been seen that sperm binds to membrane receptors that lead to a release in Ca<sup>2+</sup> from the ER. The sperm has also been observed to release a soluble factor that is specific to that species. This prevents cross species fertilization to occur. These soluble factors lead to activation of IP<sub>3</sub> which causes a Ca<sup>2+</sup> release from the ER via IP<sub>3</sub> receptors.<sup id="cite_ref-22" class="reference"><a href="#cite_note-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup> It has also been seen that some model systems mix these methods such as seen with mammals.<sup id="cite_ref-23" class="reference"><a href="#cite_note-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-24" class="reference"><a href="#cite_note-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> Once the Ca<sup>2+</sup> is released from the ER the egg starts the process of forming a fused <a href="/wiki/Pronucleus" title="Pronucleus">pronucleus</a> and the restart of the mitotic cell cycle.<sup id="cite_ref-25" class="reference"><a href="#cite_note-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup> Ca<sup>2+</sup> release is also responsible for the activation of <a href="/wiki/NAD%2B_kinase" title="NAD+ kinase">NAD<sup>+</sup> kinase</a> which leads to membrane <a href="/wiki/Biosynthesis" title="Biosynthesis">biosynthesis</a>, and the <a href="/wiki/Exocytosis" title="Exocytosis">exocytosis</a> of the oocytes <a href="/wiki/Cortical_granule" title="Cortical granule">cortical granules</a> which leads to the formation of the <a href="/wiki/Hyalin" title="Hyalin">hyaline</a> layer allowing for the slow block to <a href="/wiki/Polyspermy" title="Polyspermy">polyspermy</a>. </p> <div class="mw-heading mw-heading2"><h2 id="See_also">See also</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Calcium_signaling&action=edit&section=8" title="Edit section: See also"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li><a href="/wiki/Nanodomain" title="Nanodomain">Nanodomain</a></li> <li><a href="/wiki/European_Calcium_Society" title="European Calcium Society">European Calcium Society</a></li></ul> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Calcium_signaling&action=edit&section=9" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output 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Sunderland, Massachusetts. p. 221. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/978-1-60535-470-5" title="Special:BookSources/978-1-60535-470-5"><bdi>978-1-60535-470-5</bdi></a>. <a href="/wiki/OCLC_(identifier)" class="mw-redirect" title="OCLC (identifier)">OCLC</a> <a rel="nofollow" class="external text" href="https://search.worldcat.org/oclc/945169933">945169933</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Developmental+biology&rft.place=Sunderland%2C+Massachusetts&rft.pages=221&rft.edition=Eleventh&rft.date=2016-06-15&rft_id=info%3Aoclcnum%2F945169933&rft.isbn=978-1-60535-470-5&rft.au=Gilbert%2C+Scott+F.%2C+1949-&rfr_id=info%3Asid%2Fen.wikipedia.org%3ACalcium+signaling" class="Z3988"></span><span class="cs1-maint citation-comment"><code class="cs1-code">{{<a href="/wiki/Template:Cite_book" title="Template:Cite book">cite book</a>}}</code>: CS1 maint: location missing publisher (<a href="/wiki/Category:CS1_maint:_location_missing_publisher" title="Category:CS1 maint: location missing publisher">link</a>) CS1 maint: multiple names: authors list (<a href="/wiki/Category:CS1_maint:_multiple_names:_authors_list" title="Category:CS1 maint: multiple names: authors list">link</a>) CS1 maint: numeric names: authors list (<a href="/wiki/Category:CS1_maint:_numeric_names:_authors_list" title="Category:CS1 maint: numeric names: authors list">link</a>)</span></span> </li> </ol></div> <div class="mw-heading mw-heading2"><h2 id="Further_reading">Further reading</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Calcium_signaling&action=edit&section=10" title="Edit section: Further reading"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFPetersen2005" class="citation journal cs1">Petersen OH (2005). "Ca2+ signalling and Ca2+-activated ion channels in exocrine acinar cells". <i>Cell Calcium</i>. <b>38</b> (3–4): 171–200. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.ceca.2005.06.024">10.1016/j.ceca.2005.06.024</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/16107275">16107275</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Cell+Calcium&rft.atitle=Ca2%2B+signalling+and+Ca2%2B-activated+ion+channels+in+exocrine+acinar+cells&rft.volume=38&rft.issue=3%E2%80%934&rft.pages=171-200&rft.date=2005&rft_id=info%3Adoi%2F10.1016%2Fj.ceca.2005.06.024&rft_id=info%3Apmid%2F16107275&rft.aulast=Petersen&rft.aufirst=OH&rfr_id=info%3Asid%2Fen.wikipedia.org%3ACalcium+signaling" 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this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Signal_transduction" title="Template talk:Signal transduction"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Signal_transduction" title="Special:EditPage/Template:Signal transduction"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Cell_signaling_/_Signal_transduction" style="font-size:114%;margin:0 4em"><a href="/wiki/Cell_signaling" title="Cell signaling">Cell signaling</a> / <a href="/wiki/Signal_transduction" title="Signal transduction">Signal transduction</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%">Signaling pathways</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/G_protein-coupled_receptor" title="G protein-coupled receptor">GPCR</a></li> <li class="mw-empty-elt"></li> <li><a href="/wiki/Wnt_signaling_pathway" title="Wnt signaling pathway">Wnt</a></li> <li><a href="/wiki/Receptor_tyrosine_kinase" title="Receptor tyrosine kinase">RTK</a> <ul><li><a href="/wiki/TGF_beta_signaling_pathway" title="TGF beta signaling pathway">TGF beta</a></li> <li><a href="/wiki/MAPK/ERK_pathway" title="MAPK/ERK pathway">MAPK/ERK</a></li></ul></li> <li><a href="/wiki/Notch_signaling_pathway" title="Notch signaling pathway">Notch</a></li> <li><a href="/wiki/JAK-STAT_signaling_pathway" title="JAK-STAT signaling pathway">JAK-STAT</a></li> <li><a href="/wiki/Akt/PKB_signaling_pathway" title="Akt/PKB signaling pathway">Akt/PKB</a></li> <li><a href="/wiki/Apoptosis" title="Apoptosis">Fas apoptosis</a></li> <li><a href="/wiki/Hippo_signaling_pathway" title="Hippo signaling pathway">Hippo</a></li> <li><a href="/wiki/PI3K/AKT/mTOR_pathway" title="PI3K/AKT/mTOR pathway">PI3K/AKT/mTOR pathway</a></li> <li><a href="/wiki/Integrin#Signal_transduction" title="Integrin">Integrin receptors</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Agents</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Ligand_(biochemistry)" title="Ligand (biochemistry)">Receptor ligands</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Hormone" title="Hormone">Hormones</a></li> <li><a href="/wiki/Neurotransmitter" title="Neurotransmitter">Neurotransmitters</a>/<a href="/wiki/Neuropeptide" title="Neuropeptide">Neuropeptides</a>/<a href="/wiki/Neurohormone" title="Neurohormone">Neurohormones</a></li> <li><a href="/wiki/Cytokine" title="Cytokine">Cytokines</a></li> <li><a href="/wiki/Growth_factor" title="Growth factor">Growth factors</a></li> <li><a href="/wiki/Cell_signaling" title="Cell signaling">Signaling molecules</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Receptor_(biochemistry)" title="Receptor (biochemistry)">Receptors</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Cell_surface_receptor" title="Cell surface receptor">Cell surface</a></li> <li><a href="/wiki/Intracellular_receptor" title="Intracellular receptor">Intracellular</a></li> <li><a href="/wiki/Co-receptor" title="Co-receptor">Co-receptor</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Second_messenger_system" title="Second messenger system">Second messenger</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><td colspan="2" class="navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/CAMP-dependent_pathway" title="CAMP-dependent pathway">cAMP-dependent pathway</a></li> <li><a class="mw-selflink selflink">Ca<sup>2+</sup> signaling</a></li> <li><a href="/wiki/Lipid_signaling" title="Lipid signaling">Lipid signaling</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Assistants:</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Signal_transducing_adaptor_protein" title="Signal transducing adaptor protein">Signal transducing adaptor protein</a></li> <li><a href="/wiki/Scaffold_protein" title="Scaffold protein">Scaffold protein</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Transcription_factor" title="Transcription factor">Transcription factors</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/General_transcription_factor" title="General transcription factor">General</a></li> <li><a href="/wiki/Transcription_preinitiation_complex" title="Transcription preinitiation complex">Transcription preinitiation complex</a></li> <li><a href="/wiki/Transcription_factor_II_D" title="Transcription factor II D">TFIID</a></li> <li><a href="/wiki/Transcription_factor_II_H" title="Transcription factor II H">TFIIH</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">By distance</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Juxtacrine_signalling" title="Juxtacrine signalling">Juxtacrine</a></li> <li><a href="/wiki/Autocrine_signalling" class="mw-redirect" title="Autocrine signalling">Autocrine</a> / <a href="/wiki/Paracrine_signalling" class="mw-redirect" title="Paracrine signalling">Paracrine</a></li> <li><a href="/wiki/Endocrine_system" title="Endocrine system">Endocrine</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other concepts</th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Intracrine" title="Intracrine">Intracrine action</a></li> <li>Neurocrine signaling <ul><li><a href="/wiki/Synaptic_transmission" class="mw-redirect" title="Synaptic transmission">Synaptic transmission</a></li> <li><a href="/wiki/Chemical_synapse" title="Chemical synapse">Chemical synapse</a></li></ul></li> <li><a href="/wiki/Neuroendocrine_cell" title="Neuroendocrine cell">Neuroendocrine signaling</a></li> <li><a href="/wiki/Exocrine_gland" title="Exocrine gland">Exocrine signalling</a> <ul><li><a href="/wiki/Pheromone" title="Pheromone">Pheromones</a></li></ul></li> <li><a href="/wiki/Mechanotransduction" title="Mechanotransduction">Mechanotransduction</a></li> <li><a href="/wiki/Visual_phototransduction" title="Visual phototransduction">Phototransduction</a></li> <li><a href="/wiki/Ion_channel" title="Ion channel">Ion channel gating</a></li> <li><a href="/wiki/Gap_junction" title="Gap junction">Gap junction</a></li></ul> </div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"></div><div role="navigation" class="navbox" aria-labelledby="Cell_signaling:_calcium_signaling_and_calcium_metabolism" style="padding:3px"><table class="nowraplinks mw-collapsible mw-collapsed navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239400231"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Calcium_signaling" title="Template:Calcium signaling"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Calcium_signaling" title="Template talk:Calcium signaling"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Calcium_signaling" title="Special:EditPage/Template:Calcium signaling"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Cell_signaling:_calcium_signaling_and_calcium_metabolism" style="font-size:114%;margin:0 4em"><a href="/wiki/Cell_signaling" title="Cell signaling">Cell signaling</a>: <a class="mw-selflink selflink">calcium signaling</a> and <a href="/wiki/Calcium_metabolism" title="Calcium metabolism">calcium metabolism</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Cell_membrane" title="Cell membrane">Cell membrane</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Adhesion_molecules" class="mw-redirect" title="Adhesion molecules">Adhesion molecules</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Cadherin" title="Cadherin">Cadherins</a> <ul><li><a href="/wiki/CDH1_(gene)" class="mw-redirect" title="CDH1 (gene)">CDH1</a></li> <li><a href="/wiki/CDH2" class="mw-redirect" title="CDH2">CDH2</a></li> <li><a href="/wiki/CDH3_(gene)" title="CDH3 (gene)">CDH3</a></li> <li><a href="/wiki/CDH4" title="CDH4">CDH4</a></li> <li><a href="/wiki/CDH5" class="mw-redirect" title="CDH5">CDH5</a></li> <li><a href="/wiki/CDH6" title="CDH6">CDH6</a></li> <li><a href="/w/index.php?title=CDH7&action=edit&redlink=1" class="new" title="CDH7 (page does not exist)">CDH7</a></li> <li><a href="/wiki/CDH8" title="CDH8">CDH8</a></li> <li><a href="/wiki/CDH9" title="CDH9">CDH9</a></li> <li><a href="/wiki/CDH10" title="CDH10">CDH10</a></li> <li><a href="/wiki/CDH11" title="CDH11">CDH11</a></li> <li><a href="/wiki/CDH12" title="CDH12">CDH12</a></li> <li><a href="/wiki/CDH13" class="mw-redirect" title="CDH13">CDH13</a></li> <li><a href="/w/index.php?title=CDH14&action=edit&redlink=1" class="new" title="CDH14 (page does not exist)">CDH14</a></li> <li><a href="/wiki/CDH15" title="CDH15">CDH15</a></li> <li><a href="/wiki/CDH16" title="CDH16">CDH16</a></li> <li><a href="/wiki/CDH17" title="CDH17">CDH17</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Calcium_channel" title="Calcium channel">Calcium channels</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Ligand-gated_ion_channel" title="Ligand-gated ion channel">Ligand-gated</a> <ul><li><a href="/wiki/5-HT3_receptor" title="5-HT3 receptor">5-HT3 receptor</a></li> <li><a href="/wiki/Ionotropic_glutamate_receptor" title="Ionotropic glutamate receptor">Ionotropic glutamate receptors</a> <ul><li><a href="/wiki/AMPA_receptor" title="AMPA receptor">AMPA receptors</a></li> <li><a href="/wiki/Kainate_receptor" title="Kainate receptor">Kainate receptors</a></li> <li><a href="/wiki/NMDA_receptor" title="NMDA receptor">NMDA receptors</a></li></ul></li> <li><a href="/wiki/P2X_purinoreceptor" title="P2X purinoreceptor">P2X receptors</a></li></ul></li> <li><a href="/wiki/Voltage-gated_calcium_channel" title="Voltage-gated calcium channel">Voltage-gated</a> <ul><li><a href="/wiki/L-type_calcium_channel" title="L-type calcium channel">L</a></li> <li><a href="/wiki/N-type_calcium_channel" title="N-type calcium channel">N</a></li> <li><a href="/wiki/P-type_calcium_channel" title="P-type calcium channel">P</a></li> <li><a href="/wiki/R-type_calcium_channel" title="R-type calcium channel">R</a></li> <li><a href="/wiki/T-type_calcium_channel" title="T-type calcium channel">T</a></li></ul></li> <li><a href="/wiki/Transient_receptor_potential_channel" title="Transient receptor potential channel">TRP channels</a> <ul><li><a href="/wiki/TRPA_(ion_channel)" title="TRPA (ion channel)">TRPA</a></li> <li><a href="/wiki/TRPC" title="TRPC">TRPC</a></li> <li><a href="/wiki/TRPV" title="TRPV">TRPV</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Ion_transporter" title="Ion transporter">Calcium pumps</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Sodium-calcium_exchanger" title="Sodium-calcium exchanger">Sodium-calcium exchangers</a> <ul><li><a href="/wiki/SLC3A2" class="mw-redirect" title="SLC3A2">SLC3A2</a></li> <li><a href="/wiki/SLC8A1" class="mw-redirect" title="SLC8A1">SLC8A1</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/GPCR" class="mw-redirect" title="GPCR">GPCRs</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Calcium-sensing_receptor" title="Calcium-sensing receptor">Calcium-sensing receptor</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Annexin" title="Annexin">Annexins</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Annexin_A1" title="Annexin A1">A1</a></li> <li><a href="/wiki/Annexin_A2" title="Annexin A2">A2</a></li> <li><a href="/wiki/Annexin_A3" title="Annexin A3">A3</a></li> <li><a href="/wiki/Annexin_A4" title="Annexin A4">A4</a></li> <li><a href="/wiki/Annexin_A5" title="Annexin A5">A5</a></li> <li><a href="/wiki/Annexin_A6" title="Annexin A6">A6</a></li> <li><a href="/wiki/Annexin_A7" title="Annexin A7">A7</a></li> <li><a href="/w/index.php?title=Annexin_A8&action=edit&redlink=1" class="new" title="Annexin A8 (page does not exist)">A8</a></li> <li><a href="/wiki/ANXA8L2" title="ANXA8L2">A8-L2</a></li> <li><a href="/wiki/Annexin_A9" title="Annexin A9">A9</a></li> <li><a href="/w/index.php?title=Annexin_A10&action=edit&redlink=1" class="new" title="Annexin A10 (page does not exist)">A10</a></li> <li><a href="/wiki/Annexin_A11" title="Annexin A11">A11</a></li> <li><a href="/w/index.php?title=Annexin_A12&action=edit&redlink=1" class="new" title="Annexin A12 (page does not exist)">A12</a></li> <li><a href="/wiki/Annexin_A13" title="Annexin A13">A13</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Intracellular <a href="/wiki/Signal_transduction" title="Signal transduction">signaling</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Second_messengers" class="mw-redirect" title="Second messengers">Second messengers</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Inositol_triphosphate" class="mw-redirect" title="Inositol triphosphate">IP3</a></li> <li><a href="/wiki/Nicotinic_acid_adenine_dinucleotide_phosphate" title="Nicotinic acid adenine dinucleotide phosphate">NAADP</a></li> <li><a href="/wiki/Cyclic_ADP-ribose" title="Cyclic ADP-ribose">cADPR</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Ryanodine-Inositol_1,4,5-triphosphate_receptor_calcium_channels" title="Ryanodine-Inositol 1,4,5-triphosphate receptor calcium channels">Intracellular channels</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Inositol_trisphosphate_receptor" title="Inositol trisphosphate receptor">IP3 receptor</a></li> <li><a href="/wiki/Ryanodine_receptor" title="Ryanodine receptor">Ryanodine receptor</a> <ul><li><a href="/wiki/Calcium-induced_calcium_release" title="Calcium-induced calcium release">Calcium-induced calcium release</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Intracellular pumps</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/SERCA" title="SERCA">SERCA</a> <ul><li><a href="/wiki/ATP2A1" title="ATP2A1">ATP2A1</a></li> <li><a href="/wiki/ATP2A2" title="ATP2A2">ATP2A2</a></li> <li><a href="/wiki/ATP2A3" title="ATP2A3">ATP2A3</a></li></ul></li> <li><a href="/wiki/Sodium-calcium_exchanger" title="Sodium-calcium exchanger">Sodium-calcium exchangers</a> <ul><li><a href="/wiki/SLC8B1" title="SLC8B1">SLC8B1</a></li> <li><a href="/wiki/SLC24A5" class="mw-redirect" title="SLC24A5">SLC24A5</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Intracellular_calcium-sensing_proteins" title="Intracellular calcium-sensing proteins">Sensors</a> and <a href="/wiki/Chelator" class="mw-redirect" title="Chelator">chelators</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Calbindin" title="Calbindin">Calbindin</a></li> <li><a href="/wiki/Calmodulin" title="Calmodulin">Calmodulin</a> <ul><li><a href="/wiki/CALM1" class="mw-redirect" title="CALM1">CALM1</a></li> <li><a href="/wiki/CALM2" title="CALM2">CALM2</a></li> <li><a href="/wiki/CALM3" title="CALM3">CALM3</a></li> <li><a href="/wiki/CALML3" title="CALML3">CALML3</a></li> <li><a href="/wiki/CALML5" title="CALML5">CALML5</a></li></ul></li> <li><a href="/wiki/Calsequestrin" title="Calsequestrin">Calsequestrin</a></li> <li><a href="/wiki/Calretinin" title="Calretinin">Calretinin</a></li> <li><a href="/wiki/Gelsolin" title="Gelsolin">Gelsolin</a></li> <li><a href="/wiki/Neuronal_calcium_sensor" title="Neuronal calcium sensor">Neuronal calcium sensors</a> <ul><li><a href="/wiki/Calsenilin" title="Calsenilin">Calsenilin</a></li> <li><a href="/wiki/Frequenin" class="mw-redirect" title="Frequenin">Frequenin</a></li> <li><a href="/wiki/Guanylate_cyclase_activator" title="Guanylate cyclase activator">GUCA</a> <ul><li><a href="/wiki/GUCA1A" title="GUCA1A">1A</a></li> <li><a href="/wiki/GUCA1B" title="GUCA1B">1B</a></li></ul></li> <li><a href="/wiki/Hippocalcin" title="Hippocalcin">Hippocalcin</a></li> <li><a href="/wiki/Neurocalcin" title="Neurocalcin">Neurocalcin</a></li> <li><a href="/wiki/Recoverin" title="Recoverin">Recoverin</a></li> <li><a href="/wiki/VSNL1" class="mw-redirect" title="VSNL1">Visinin</a></li></ul></li> <li><a href="/wiki/Parvalbumin" title="Parvalbumin">Parvalbumin</a></li> <li><a href="/wiki/Phospholamban" title="Phospholamban">Phospholamban</a></li> <li><a href="/wiki/Sarcalumenin" title="Sarcalumenin">Sarcalumenin</a></li> <li><a href="/wiki/Synaptotagmin" title="Synaptotagmin">Synaptotagmins</a> <ul><li><a href="/wiki/SYT1" title="SYT1">SYT1</a></li> <li><a href="/wiki/SYT2" title="SYT2">SYT2</a></li> <li><a href="/wiki/SYT3" title="SYT3">SYT3</a></li> <li><a href="/wiki/SYT4" title="SYT4">SYT4</a></li> <li><a href="/wiki/SYT5" title="SYT5">SYT5</a></li> <li><a href="/wiki/SYT6" title="SYT6">SYT6</a></li> <li><a href="/wiki/SYT7" title="SYT7">SYT7</a></li> <li><a href="/wiki/SYT9" title="SYT9">SYT9</a></li> <li><a href="/wiki/SYT11" title="SYT11">SYT11</a></li> <li><a href="/wiki/SYT13" title="SYT13">SYT13</a></li> <li><a href="/wiki/SYT14" class="mw-redirect" title="SYT14">SYT14</a></li></ul></li> <li><a href="/wiki/S100_protein" title="S100 protein">S100</a></li> <li><a href="/wiki/S100P" title="S100P">S100P</a></li> <li><a href="/wiki/Troponin_C" title="Troponin C">Troponin C</a> <ul><li><a href="/wiki/TNNC1" class="mw-redirect" title="TNNC1">TNNC1</a></li> <li><a href="/wiki/TNNC2" class="mw-redirect" title="TNNC2">TNNC2</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Calcium-dependent <a href="/wiki/Chaperone_(protein)" title="Chaperone (protein)">chaperones</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Calreticulin" title="Calreticulin">Calreticulin</a></li> <li><a href="/wiki/Calnexin" title="Calnexin">Calnexin</a></li> <li><a href="/wiki/HSPA5" class="mw-redirect" title="HSPA5">HSPA5</a></li> <li><a href="/wiki/HSP90B1" title="HSP90B1">HSP90B1</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Calcium-dependent <a href="/wiki/Kinase" title="Kinase">kinases</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Calmodulin-dependent_kinase" class="mw-redirect" title="Calmodulin-dependent kinase">CaM kinases</a> <ul><li><a href="/wiki/CAMK1" title="CAMK1">CAMK1</a></li> <li><a href="/wiki/CAMKII" class="mw-redirect" title="CAMKII">CAMK2</a> <ul><li><a href="/wiki/CAMK2A" class="mw-redirect" title="CAMK2A">A</a></li> <li><a href="/wiki/CAMK2B" title="CAMK2B">B</a></li> <li><a href="/wiki/CAMK2D" title="CAMK2D">D</a></li> <li><a href="/wiki/CAMK2G" title="CAMK2G">G</a></li></ul></li> <li><a href="/wiki/EEF2K" title="EEF2K">CAMK3</a></li> <li><a href="/wiki/CAMK4" title="CAMK4">CAMK4</a></li></ul></li> <li><a href="/wiki/Protein_kinase_C" title="Protein kinase C">Protein kinase C</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Calcium-dependent <a href="/wiki/Protease" title="Protease">proteases</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Calpain" title="Calpain">Calpains</a> <ul><li><a href="/wiki/CAPN1" class="mw-redirect" title="CAPN1">CAPN1</a></li> <li><a href="/wiki/CAPN2" class="mw-redirect" title="CAPN2">CAPN2</a></li> <li><a href="/wiki/CAPN3" class="mw-redirect" title="CAPN3">CAPN3</a></li> <li><a href="/wiki/CAPNS1" class="mw-redirect" title="CAPNS1">CAPN4</a></li> <li><a href="/wiki/CAPN5" title="CAPN5">CAPN5</a></li> <li><a href="/wiki/CAPN6" class="mw-redirect" title="CAPN6">CAPN6</a></li> <li><a href="/w/index.php?title=CAPN7&action=edit&redlink=1" class="new" title="CAPN7 (page does not exist)">CAPN7</a></li> <li><a href="/wiki/CAPN8" class="mw-redirect" title="CAPN8">CAPN8</a></li> <li><a href="/wiki/CAPN9" class="mw-redirect" title="CAPN9">CAPN9</a></li> <li><a href="/wiki/CAPN10" title="CAPN10">CAPN10</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Indirect regulators</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Calcitonin" title="Calcitonin">Calcitonin</a></li> <li><a href="/wiki/Parathyroid_hormone" title="Parathyroid hormone">Parathyroid hormone</a></li> <li><a href="/wiki/Vitamin_D" title="Vitamin D">Vitamin D</a></li> <li><a href="/wiki/Vitamin_K" title="Vitamin K">Vitamin K</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Extracellular <a href="/wiki/Chelation" title="Chelation">chelators</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Extracellular_matrix" title="Extracellular matrix">Extracellular matrix</a> proteins</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Fibulin" title="Fibulin">Fibulins</a> <ul><li><a href="/wiki/FBLN1" title="FBLN1">FBLN1</a></li> <li><a href="/wiki/FBLN2" title="FBLN2">FBLN2</a></li> <li><a href="/wiki/FBLN3" class="mw-redirect" title="FBLN3">FBLN3</a></li> <li><a href="/wiki/FBLN4" class="mw-redirect" title="FBLN4">FBLN4</a></li> <li><a href="/wiki/FBLN5" title="FBLN5">FBLN5</a></li></ul></li> <li><a href="/wiki/Hemicentin_1" title="Hemicentin 1">Hemicentin 1</a></li> <li><a href="/wiki/Matrix_gla_protein" class="mw-redirect" title="Matrix gla protein">Matrix gla protein</a></li> <li><a href="/wiki/Osteonectin" title="Osteonectin">Osteonectin</a></li> <li><a href="/wiki/SIBLING_proteins" title="SIBLING proteins">SIBLINGs</a> <ul><li><a href="/wiki/Bone_sialoprotein" title="Bone sialoprotein">Bone sialoprotein</a></li> <li><a href="/wiki/DMP1" title="DMP1">Dentin matrix phosphoprotein</a></li> <li><a href="/wiki/Dentin_sialophosphoprotein" title="Dentin sialophosphoprotein">Dentin sialophosphoprotein</a></li> <li><a href="/wiki/Osteopontin" title="Osteopontin">Osteopontin</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Hormone" title="Hormone">Secreted hormones</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Osteocalcin" title="Osteocalcin">Osteocalcin</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Calcium-binding <a href="/wiki/Protein_domain" title="Protein domain">domains</a></th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/C2_domain" title="C2 domain">C2 domain</a></li> <li><a href="/wiki/Cadherin" title="Cadherin">Cadherin</a></li> <li><a href="/wiki/C-type_lectin" title="C-type lectin">C-type lectin</a></li> <li><a href="/wiki/EF_hand" title="EF hand">EF hand</a></li> <li><a href="/wiki/EGF-like_domain" title="EGF-like domain">EGF-like domain</a></li> <li><a href="/wiki/Gla_domain" title="Gla domain">Gla domain</a></li></ul> </div></td></tr></tbody></table></div>    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