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Modal Gating of Human Ca(V)2.1 (P/Q-type) Calcium Channels: I. The Slow and the Fast Gating Modes and their Modulation by β Subunits
The single channel gating properties of human Ca(V)2.1 (P/Q-type) calcium channels and their modulation by the auxiliary β(1b), β(2e), β(3a), and β(4a) subunits were investigated with cell-attached patch-clamp recordings on HEK293 cells stably expressing human Ca(V)2.1 channels. These calcium channe...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2004
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2234000/ https://www.ncbi.nlm.nih.gov/pubmed/15504896 http://dx.doi.org/10.1085/jgp.200409034 |
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author | Luvisetto, Siro Fellin, Tommaso Spagnolo, Michele Hivert, Bruno Brust, Paul F. Harpold, Michael M. Stauderman, Kenneth A. Williams, Mark E. Pietrobon, Daniela |
author_facet | Luvisetto, Siro Fellin, Tommaso Spagnolo, Michele Hivert, Bruno Brust, Paul F. Harpold, Michael M. Stauderman, Kenneth A. Williams, Mark E. Pietrobon, Daniela |
author_sort | Luvisetto, Siro |
collection | PubMed |
description | The single channel gating properties of human Ca(V)2.1 (P/Q-type) calcium channels and their modulation by the auxiliary β(1b), β(2e), β(3a), and β(4a) subunits were investigated with cell-attached patch-clamp recordings on HEK293 cells stably expressing human Ca(V)2.1 channels. These calcium channels showed a complex modal gating, which is described in this and the following paper (Fellin, T., S. Luvisetto, M. Spagnolo, and D. Pietrobon. 2004. J. Gen. Physiol. 124:463–474). Here, we report the characterization of two modes of gating of human Ca(V)2.1 channels, the slow mode and the fast mode. A channel in the two gating modes differs in mean closed times and latency to first opening (both longer in the slow mode), in voltage dependence of the open probability (larger depolarizations are necessary to open the channel in the slow mode), in kinetics of inactivation (slower in the slow mode), and voltage dependence of steady-state inactivation (occurring at less negative voltages in the slow mode). Ca(V)2.1 channels containing any of the four β subtypes can gate in either the slow or the fast mode, with only minor differences in the rate constants of the transitions between closed and open states within each mode. In both modes, Ca(V)2.1 channels display different rates of inactivation and different steady-state inactivation depending on the β subtype. The type of β subunit also modulates the relative occurrence of the slow and the fast gating mode of Ca(V)2.1 channels; β(3a) promotes the fast mode, whereas β(4a) promotes the slow mode. The prevailing mode of gating of Ca(V)2.1 channels lacking a β subunit is a gating mode in which the channel shows shorter mean open times, longer mean closed times, longer first latency, a much larger fraction of nulls, and activates at more positive voltages than in either the fast or slow mode. |
format | Text |
id | pubmed-2234000 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22340002008-03-21 Modal Gating of Human Ca(V)2.1 (P/Q-type) Calcium Channels: I. The Slow and the Fast Gating Modes and their Modulation by β Subunits Luvisetto, Siro Fellin, Tommaso Spagnolo, Michele Hivert, Bruno Brust, Paul F. Harpold, Michael M. Stauderman, Kenneth A. Williams, Mark E. Pietrobon, Daniela J Gen Physiol Article The single channel gating properties of human Ca(V)2.1 (P/Q-type) calcium channels and their modulation by the auxiliary β(1b), β(2e), β(3a), and β(4a) subunits were investigated with cell-attached patch-clamp recordings on HEK293 cells stably expressing human Ca(V)2.1 channels. These calcium channels showed a complex modal gating, which is described in this and the following paper (Fellin, T., S. Luvisetto, M. Spagnolo, and D. Pietrobon. 2004. J. Gen. Physiol. 124:463–474). Here, we report the characterization of two modes of gating of human Ca(V)2.1 channels, the slow mode and the fast mode. A channel in the two gating modes differs in mean closed times and latency to first opening (both longer in the slow mode), in voltage dependence of the open probability (larger depolarizations are necessary to open the channel in the slow mode), in kinetics of inactivation (slower in the slow mode), and voltage dependence of steady-state inactivation (occurring at less negative voltages in the slow mode). Ca(V)2.1 channels containing any of the four β subtypes can gate in either the slow or the fast mode, with only minor differences in the rate constants of the transitions between closed and open states within each mode. In both modes, Ca(V)2.1 channels display different rates of inactivation and different steady-state inactivation depending on the β subtype. The type of β subunit also modulates the relative occurrence of the slow and the fast gating mode of Ca(V)2.1 channels; β(3a) promotes the fast mode, whereas β(4a) promotes the slow mode. The prevailing mode of gating of Ca(V)2.1 channels lacking a β subunit is a gating mode in which the channel shows shorter mean open times, longer mean closed times, longer first latency, a much larger fraction of nulls, and activates at more positive voltages than in either the fast or slow mode. The Rockefeller University Press 2004-11 /pmc/articles/PMC2234000/ /pubmed/15504896 http://dx.doi.org/10.1085/jgp.200409034 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Luvisetto, Siro Fellin, Tommaso Spagnolo, Michele Hivert, Bruno Brust, Paul F. Harpold, Michael M. Stauderman, Kenneth A. Williams, Mark E. Pietrobon, Daniela Modal Gating of Human Ca(V)2.1 (P/Q-type) Calcium Channels: I. The Slow and the Fast Gating Modes and their Modulation by β Subunits |
title | Modal Gating of Human Ca(V)2.1 (P/Q-type) Calcium Channels: I. The Slow and the Fast Gating Modes and their Modulation by β Subunits |
title_full | Modal Gating of Human Ca(V)2.1 (P/Q-type) Calcium Channels: I. The Slow and the Fast Gating Modes and their Modulation by β Subunits |
title_fullStr | Modal Gating of Human Ca(V)2.1 (P/Q-type) Calcium Channels: I. The Slow and the Fast Gating Modes and their Modulation by β Subunits |
title_full_unstemmed | Modal Gating of Human Ca(V)2.1 (P/Q-type) Calcium Channels: I. The Slow and the Fast Gating Modes and their Modulation by β Subunits |
title_short | Modal Gating of Human Ca(V)2.1 (P/Q-type) Calcium Channels: I. The Slow and the Fast Gating Modes and their Modulation by β Subunits |
title_sort | modal gating of human ca(v)2.1 (p/q-type) calcium channels: i. the slow and the fast gating modes and their modulation by β subunits |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2234000/ https://www.ncbi.nlm.nih.gov/pubmed/15504896 http://dx.doi.org/10.1085/jgp.200409034 |
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