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Cooh-Terminal Truncated Alpha(1S) Subunits Conduct Current Better than Full-Length Dihydropyridine Receptors

Skeletal muscle dihydropyridine (DHP) receptors function both as voltage-activated Ca(2+) channels and as voltage sensors for coupling membrane depolarization to release of Ca(2+) from the sarcoplasmic reticulum. In skeletal muscle, the principal or α(1S) subunit occurs in full-length (∼10% of total...

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Autores principales: Morrill, James A., Cannon, Stephen C.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2233682/
https://www.ncbi.nlm.nih.gov/pubmed/10962012
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author Morrill, James A.
Cannon, Stephen C.
author_facet Morrill, James A.
Cannon, Stephen C.
author_sort Morrill, James A.
collection PubMed
description Skeletal muscle dihydropyridine (DHP) receptors function both as voltage-activated Ca(2+) channels and as voltage sensors for coupling membrane depolarization to release of Ca(2+) from the sarcoplasmic reticulum. In skeletal muscle, the principal or α(1S) subunit occurs in full-length (∼10% of total) and post-transcriptionally truncated (∼90%) forms, which has raised the possibility that the two functional roles are subserved by DHP receptors comprised of different sized α(1S) subunits. We tested the functional properties of each form by injecting oocytes with cRNAs coding for full-length (α(1S)) or truncated (α(1SΔC)) α subunits. Both translation products were expressed in the membrane, as evidenced by increases in the gating charge (Q(max) 80–150 pC). Thus, oocytes provide a robust expression system for the study of gating charge movement in α(1S), unencumbered by contributions from other voltage-gated channels or the complexities of the transverse tubules. As in recordings from skeletal muscle, for heterologously expressed channels the peak inward Ba(2+) currents were small relative to Q(max). The truncated α(1SΔC) protein, however, supported much larger ionic currents than the full-length product. These data raise the possibility that DHP receptors containing the more abundant, truncated form of the α(1S) subunit conduct the majority of the L-type Ca(2+) current in skeletal muscle. Our data also suggest that the carboxyl terminus of the α(1S) subunit modulates the coupling between charge movement and channel opening.
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spelling pubmed-22336822008-04-21 Cooh-Terminal Truncated Alpha(1S) Subunits Conduct Current Better than Full-Length Dihydropyridine Receptors Morrill, James A. Cannon, Stephen C. J Gen Physiol Original Article Skeletal muscle dihydropyridine (DHP) receptors function both as voltage-activated Ca(2+) channels and as voltage sensors for coupling membrane depolarization to release of Ca(2+) from the sarcoplasmic reticulum. In skeletal muscle, the principal or α(1S) subunit occurs in full-length (∼10% of total) and post-transcriptionally truncated (∼90%) forms, which has raised the possibility that the two functional roles are subserved by DHP receptors comprised of different sized α(1S) subunits. We tested the functional properties of each form by injecting oocytes with cRNAs coding for full-length (α(1S)) or truncated (α(1SΔC)) α subunits. Both translation products were expressed in the membrane, as evidenced by increases in the gating charge (Q(max) 80–150 pC). Thus, oocytes provide a robust expression system for the study of gating charge movement in α(1S), unencumbered by contributions from other voltage-gated channels or the complexities of the transverse tubules. As in recordings from skeletal muscle, for heterologously expressed channels the peak inward Ba(2+) currents were small relative to Q(max). The truncated α(1SΔC) protein, however, supported much larger ionic currents than the full-length product. These data raise the possibility that DHP receptors containing the more abundant, truncated form of the α(1S) subunit conduct the majority of the L-type Ca(2+) current in skeletal muscle. Our data also suggest that the carboxyl terminus of the α(1S) subunit modulates the coupling between charge movement and channel opening. The Rockefeller University Press 2000-09-01 /pmc/articles/PMC2233682/ /pubmed/10962012 Text en © 2000 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 Original Article
Morrill, James A.
Cannon, Stephen C.
Cooh-Terminal Truncated Alpha(1S) Subunits Conduct Current Better than Full-Length Dihydropyridine Receptors
title Cooh-Terminal Truncated Alpha(1S) Subunits Conduct Current Better than Full-Length Dihydropyridine Receptors
title_full Cooh-Terminal Truncated Alpha(1S) Subunits Conduct Current Better than Full-Length Dihydropyridine Receptors
title_fullStr Cooh-Terminal Truncated Alpha(1S) Subunits Conduct Current Better than Full-Length Dihydropyridine Receptors
title_full_unstemmed Cooh-Terminal Truncated Alpha(1S) Subunits Conduct Current Better than Full-Length Dihydropyridine Receptors
title_short Cooh-Terminal Truncated Alpha(1S) Subunits Conduct Current Better than Full-Length Dihydropyridine Receptors
title_sort cooh-terminal truncated alpha(1s) subunits conduct current better than full-length dihydropyridine receptors
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2233682/
https://www.ncbi.nlm.nih.gov/pubmed/10962012
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