Structure and Regulation of Voltage-Gated Ca 2+ Channels

Catterall, William A.

doi:10.1146/annurev.cellbio.16.1.521

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

Structure and Regulation of Voltage-Gated Ca 2+ Channels

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

DOI 10.1146/annurev.cellbio.16.1.521

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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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Cch1 is not voltage-gated, supported by previous findings that Cch1 in C. neoformans lacks the conserved voltage sensor motif.
“Our results indicate that Cch1 is not voltage-gated, and this is further supported by our previous findings demonstrating that the protein sequence of Cch1 in C. neoformans lacks the highly conserved voltage sensor motif, the hallmark of all voltage-gated channels in eukaryotic cells (7,(35)(36)(37).”
From Cch1 Restores Intracellular Ca2+ in Fungal Cells during Endoplasmic Reticulum Stress (2010) · cites this paper as [35]
Two theories have been proposed for how electromagnetic fields modulate Cav2+ channels: depolarization of the cell membrane, and direct action on the charged residues in the voltage-sensing S4 segment adjacent to the pore.
“To answer the first question, two theories have been proposed for how electromagnetic fields modulate Cav2+ channels: (1) by depolarization of the cell membrane, which is typically employed in mechanism of action explanations of voltage-gated ion channels such as Nav+, Kv+, and Cav2+ [48] and (2) by direct action on the charged residues in the voltage-sensing S4 segment adjacent to the pore that”
From Permeabilizing Cell Membranes with Electric Fields (2021) · cites this paper as [49]

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Self-citation

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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