Calcium Influx through Voltage-gated Calcium Channels

Stable Identifier
Reaction [transition]
Homo sapiens
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Voltage-gated calcium channels respond to a change in voltage across the plasma membrane by opening and allowing free movement of calcium ions. In an unstimulated cell the concentration of calcium ions outside the cells is higher than inside due to calcium transporters so channel opening results in an influx of calcium into the cytosol. In the cytosol the calcium ions cause an immediate exocytosis of the readily releasable pool of docked insulin granules as well as a migration of reserve granules toward the plasma membrane where they will be released during the second, sustained phase of insulin secretion.
Mouse and human beta cells are known to contain L type channels Cav1.2 and Cav1.3, both of which have been shown to physically associate with docked insulin granules via Syntaxin1A. Cav1.2 and Cav1.3 predominate in the initial rapid release of insulin. Human beta cells also contain the P/Q type channel Cav2.1 and the R type channel Cav2.3. Cav2.3 is involved in regulating the second, sustained phase of insulin release but signaling and regulatory differences between the two phases of secretion are not fully characterized. Human cells also exhibit T-type (brief burst) calcium currents but the responsible channel has not been identified.
Literature References
PubMed ID Title Journal Year
17660294 The role of distal S6 hydrophobic residues in the voltage-dependent gating of CaV2.3 channels

Dionne, F, Raybaud, A, Baspinar, EE, Sauvé, R, Dodier, Y, Parent, L

J Biol Chem 2007
15504896 Modal gating of human CaV2.1 (P/Q-type) calcium channels: I. The slow and the fast gating modes and their modulation by beta subunits

Brust, PF, Fellin, T, Harpold, MM, Luvisetto, S, Williams, ME, Hivert, B, Pietrobon, D, Spagnolo, M, Stauderman, KA

J Gen Physiol 2004
11815462 A subset of 50 secretory granules in close contact with L-type Ca2+ channels accounts for first-phase insulin secretion in mouse beta-cells

Renström, E, Eliasson, L, Rorsman, P, Barg, S

Diabetes 2002
16513675 Characterization of voltage-dependent sodium and calcium channels in mouse pancreatic A- and B-cells

Welling, A, Hofmann, F, Vignali, S, Leiss, V, Karl, R

J Physiol 2006
15000528 Voltage-operated calcium channel heterogeneity in pancreatic beta cells: physiopathological implications

Carrera, P, Passafaro, M, Craig, P, Giorgi-Rossi, P, Volsen, S, Sher, E, Davalli, A, Codignola, A, Giovannini, F

J Bioenerg Biomembr 2003
1309948 Cloning of the alpha 1 subunit of a voltage-dependent calcium channel expressed in pancreatic beta cells

Blondel, O, Seino, M, Takeda, J, Bell, GI, Johnson, JH, Seino, S, Chen, L

Proc Natl Acad Sci U S A 1992
11815460 Signals and pools underlying biphasic insulin secretion

Nenquin, M, Ravier, MA, Ishiyama, N, Jonas, JC, Henquin, JC

Diabetes 2002
10424882 Immunohistochemical detection of alpha1E voltage-gated Ca(2+) channel isoforms in cerebellum, INS-1 cells, and neuroendocrine cells of the digestive system

Hescheler, J, Vajna, R, Pereverzev, A, Schneider, T, Volsen, SG, Grabsch, H, Klöckner, U, Weiergräber, M, Schramm, M, Beattie, RE, Henry, M

J Histochem Cytochem 1999
15585596 Beta-cell CaV channel regulation in physiology and pathophysiology

Berggren, PO, Yang, SN

Am J Physiol Endocrinol Metab 2005
16868246 The role of voltage-gated calcium channels in pancreatic beta-cell physiology and pathophysiology

Berggren, PO, Yang, SN

Endocr Rev 2006
11815463 Triggering and augmentation mechanisms, granule pools, and biphasic insulin secretion

Straub, SG, Yajima, H, Gunawardana, S, Sharp, GW, Daniel, S, Bratanova-Tochkova, TK, Mulvaney-Musa, J, Cheng, H, Schermerhorn, T, Liu, YJ

Diabetes 2002
Catalyst Activity

voltage-gated calcium channel activity of Voltage-gated Calcium Channels (pancreatic beta cell) [plasma membrane]

Orthologous Events
Cross References
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