Structure and Regulation of Voltage-Gated Ca<sup>2+</sup> Channels

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  • William A. Catterall
    Department of Pharmacology, Box 357280, University of Washington, Seattle, Washington 98195-7280;

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<jats:p> ▪ Abstract  Voltage-gated Ca<jats:sup>2+</jats:sup> channels mediate Ca<jats:sup>2+</jats:sup> entry into cells in response to membrane depolarization. Electrophysiological studies reveal different Ca<jats:sup>2+</jats:sup> currents designated L-, N-, P-, Q-, R-, and T-type. The high-voltage-activated Ca<jats:sup>2+</jats:sup> channels that have been characterized biochemically are complexes of a pore-forming α<jats:sub>1</jats:sub> subunit of ∼190–250 kDa; a transmembrane, disulfide-linked complex of α<jats:sub>2</jats:sub> and δ subunits; an intracellular β subunit; and in some cases a transmembrane γ subunit. Ten α<jats:sub>1</jats:sub> subunits, four α<jats:sub>2</jats:sub>δ complexes, four β subunits, and two γ subunits are known. The Ca<jats:sub>v</jats:sub>1 family of α<jats:sub>1</jats:sub> subunits conduct L-type Ca<jats:sup>2+</jats:sup> currents, which initiate muscle contraction, endocrine secretion, and gene transcription, and are regulated primarily by second messenger-activated protein phosphorylation pathways. The Ca<jats:sub>v</jats:sub>2 family of α<jats:sub>1</jats:sub> subunits conduct N-type, P/Q-type, and R-type Ca<jats:sup>2+</jats:sup> currents, which initiate rapid synaptic transmission and are regulated primarily by direct interaction with G proteins and SNARE proteins and secondarily by protein phosphorylation. The Ca<jats:sub>v</jats:sub>3 family of α<jats:sub>1</jats:sub> subunits conduct T-type Ca<jats:sup>2+</jats:sup> currents, which are activated and inactivated more rapidly and at more negative membrane potentials than other Ca<jats:sup>2+</jats:sup> current types. The distinct structures and patterns of regulation of these three families of Ca<jats:sup>2+</jats:sup> channels provide a flexible array of Ca<jats:sup>2+</jats:sup> entry pathways in response to changes in membrane potential and a range of possibilities for regulation of Ca<jats:sup>2+</jats:sup> entry by second messenger pathways and interacting proteins. </jats:p>

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