Cited by 2,344Ion channel regulation and functionCardiac electrophysiology and arrhythmiasIon Channels and Receptors

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Structure and Regulation of Voltage-Gated Ca 2+ Channels

Catterall, William A.·2000·Annual Review of Cell and Developmental Biology

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Abstract

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

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Authors: Catterall, W. A.
Affiliations: University of Washington (US)
Corresponding author: Catterall, William A.
ORCID: Catterall, William A.
Venue: Annual Review of Cell and Developmental Biology
Publisher: Annual Reviews
Published: 2000-11
Volume: 16
Issue: 1
Pages: 521-555
ISSN: 1081-0706 (ISSN-L)
1530-8995
DOI: 10.1146/annurev.cellbio.16.1.521
OpenAlex: W2112520390
Cited by: 2,344
References: 226
Citations by year: 2026: 20 · 2025: 24 · 2024: 38 · 2023: 37 · 2022: 60 · 2021: 47 · 2020: 90 · 2019: 57 · 2018: 55 · 2017: 71 · 2016: 65 · 2015: 72 · 2014: 122 · 2013: 123 · 2012: 134
FWCI: 5.88
Type: journal article
Language: en
Open access: closed
Locations: Annual Review of Cell and Developmental Biology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Keywords: voltage-gated calcium channels, calcium channel subunits, L-type calcium current, N-type calcium current, T-type calcium current, alpha1 subunit, alpha2delta subunit, beta subunit, gamma subunit, protein phosphorylation, second messenger signaling, G protein coupling, SNARE proteins, synaptic transmission, calcium influx
MeSH terms: Animals, Calcium, Electrophysiology, Humans, Intracellular Fluid, Phosphorylation, Proteins, Calcium Channels, GTP-Binding Proteins

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Structure and Regulation of Voltage-Gated Ca 2+ Channels

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