Functional impacts of the skeletal muscle-specific Ca2+ channel subunit γ1 have previously been studied using coexpression with the cardiac α1C polypeptide in nonmuscle cells and primary-cultured myotubes of γ1-deficient mice. Data from single adult muscle fibers of γ−/− mice are not yet available. In the present study, we performed voltage clamp experiments on enzymatically isolated mature muscle fibers of the m. interosseus obtained from γ+/+ and γ−/− mice. We measured L-type Ca2+ inward currents and intracellular Ca2+ transients during 100-ms step depolarizations from a holding potential of −80 mV. Ratiometric Ca2+ transients were analyzed with a removal model fit approach to calculate the flux of Ca2+ from the sarcoplasmic reticulum. Ca2+ current density, Ca2+ release flux, and the voltage dependence of activation of both Ca2+ current and Ca2+ release were not significantly different. By varying the holding potential and recording Ca2+ current and Ca2+ release flux induced by 100-ms test depolarizations to +20 mV, we studied quasi-steady-state properties of slow voltage–dependent inactivation. For the Ca2+ current, these experiments showed a right-shifted voltage dependence of inactivation. Importantly, we could demonstrate that a very similar shift occurred also in the inactivation curve of Ca2+ release. Voltages of half maximal inactivation were altered by 16 (current) and 14 mV (release), respectively. Muscle fiber bundles, activated by elevated potassium concentration (120 mM), developed about threefold larger contracture force in γ−/− compared with γ+/+. This difference was independent of the presence of extracellular Ca2+ and likely results from the lower sensitivity to voltage-dependent inactivation of Ca2+ release. These results demonstrate a specific alteration of voltage-dependent inactivation of both Ca2+ entry and Ca2+ release by the γ1 subunit of the dihydropyridine receptor in mature muscle fibers of the mouse.
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1 November 2004
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October 25 2004
Altered Inactivation of Ca2+ Current and Ca2+ Release in Mouse Muscle Fibers Deficient in the DHP receptor γ1 subunit
Daniel Ursu,
Daniel Ursu
1Universität Ulm, Abteilung für Angewandte Physiologie, D-89069 Ulm, Germany
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Ralph Peter Schuhmeier,
Ralph Peter Schuhmeier
1Universität Ulm, Abteilung für Angewandte Physiologie, D-89069 Ulm, Germany
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Marc Freichel,
Marc Freichel
2Institut für Pharmakologie und Toxikologie, Universität des Saarlandes, D-66421 Homburg, Germany
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Veit Flockerzi,
Veit Flockerzi
2Institut für Pharmakologie und Toxikologie, Universität des Saarlandes, D-66421 Homburg, Germany
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Werner Melzer
Werner Melzer
1Universität Ulm, Abteilung für Angewandte Physiologie, D-89069 Ulm, Germany
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Daniel Ursu
1Universität Ulm, Abteilung für Angewandte Physiologie, D-89069 Ulm, Germany
Ralph Peter Schuhmeier
1Universität Ulm, Abteilung für Angewandte Physiologie, D-89069 Ulm, Germany
Marc Freichel
2Institut für Pharmakologie und Toxikologie, Universität des Saarlandes, D-66421 Homburg, Germany
Veit Flockerzi
2Institut für Pharmakologie und Toxikologie, Universität des Saarlandes, D-66421 Homburg, Germany
Werner Melzer
1Universität Ulm, Abteilung für Angewandte Physiologie, D-89069 Ulm, Germany
Address correspondence to Werner Melzer, University of Ulm, Dept. of Applied Physiology, Albert-Einstein-Allee 11, D-89069 Ulm, Germany. Fax: 49-731-500-23260; email: [email protected]
Abbreviations used in this paper: DHPR, dihydropyridine receptor; EDL, extensor digitorum longus; RyR, ryanodine receptor; SR, sarcoplasmic reticulum.
Received:
August 13 2004
Accepted:
October 04 2004
Online ISSN: 1540-7748
Print ISSN: 0022-1295
The Rockefeller University Press
2004
J Gen Physiol (2004) 124 (5): 605–618.
Article history
Received:
August 13 2004
Accepted:
October 04 2004
Citation
Daniel Ursu, Ralph Peter Schuhmeier, Marc Freichel, Veit Flockerzi, Werner Melzer; Altered Inactivation of Ca2+ Current and Ca2+ Release in Mouse Muscle Fibers Deficient in the DHP receptor γ1 subunit . J Gen Physiol 1 November 2004; 124 (5): 605–618. doi: https://doi.org/10.1085/jgp.200409168
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