title: Voltage-gated calcium channels function as Ca2+-activated signaling receptors.
abstract: Voltage-gated calcium channels (VGCCs) are transmembrane cell surface proteins responsible for multifunctional signals. In response to voltage, VGCCs trigger synaptic transmission, drive muscle contraction, and regulate gene expression. Voltage perturbations open VGCCs enabling Ca(2+) binding to the low affinity Ca(2+) binding site of the channel pore. Subsequent to permeation, Ca(2+) targets selective proteins to activate diverse signaling pathways. It is becoming apparent that the Ca(2+)-bound channel triggers secretion in excitable cells and drives contraction in cardiomyocytes prior to Ca(2+) permeation. Here, I highlight recent data implicating receptor-like function of the Ca(2+)-bound channel in converting external Ca(2+) into an intracellular signal. The two sequential mechanistic perspectives of VGCC function are discussed in the context of the prevailing and long-standing current models of depolarization-evoked secretion and cardiac contraction.
authors.affiliation: Department of Biological Chemistry, The Alexander Silverman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 91904 Israel. Electronic address: daphne.atlas@mail.huji.ac.il.
authors.forename: Daphne
authors.initials: D
authors.lastname: Atlas
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D056966:Excitation Contraction Coupling / Q000502:physiology; D005089:Exocytosis; D015870:Gene Expression; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D050863:Synaptotagmin I / Q000235:genetics / Q000378:metabolism; D050827:Syntaxin 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D011956:Receptors, Cell Surface; D019837:Ryanodine Receptor Calcium Release Channel; C494310:SYT1 protein, human; D050863:Synaptotagmin I; D050827:Syntaxin 1; D002118:Calcium
keywords: RyR2; SNAREs; cardiac channel; cardiac contraction; ryanodine receptor; synaptotagmin; syntaxin; transmitter release