Regulation of Muscle Cav1.1 Channels by Long-term Depolarization Involves Proteolysis of the α1s Subunit

Regulation of Muscle Cav1.1 Channels by Long-term Depolarization Involves Proteolysis of the α1s... The effects of long-term depolarization on frog skeletal muscle Cav1.1 channels were assessed. Voltage-clamp and Western-blot experiments revealed that long-term depolarization brings about a drastic reduction in the amplitude of currents flowing through Cav1.1 channels and in the levels of the α1s subunit, the main subunit of muscle L-type channels. The decline of both phenomena was prevented by the action of the protease inhibitors E64 (50 μM) and leupeptin (50 μM). In contrast, long-term depolarization had no effect on β1, the auxiliary subunit of α1s. The levels of mRNAs coding the α1s and the β1 subunits were measured by RNase protection assays. Neither the content of the α1s nor the β1 subunit mRNAs were affected by long-term depolarization, indicating that the synthesis of Cav1.1 channels remained unaffected. Taken together, our experiments suggest that the reduction in the amplitude of membrane currents and in the α1s subunit levels is caused by increased degradation of this subunit by a Ca2+-dependent protease. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Regulation of Muscle Cav1.1 Channels by Long-term Depolarization Involves Proteolysis of the α1s Subunit

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Publisher
Springer-Verlag
Copyright
Copyright © 2004 by Springer-Verlag
Subject
Life Sciences; Human Physiology; Biochemistry, general
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s00232-004-0683-x
Publisher site
See Article on Publisher Site

Abstract

The effects of long-term depolarization on frog skeletal muscle Cav1.1 channels were assessed. Voltage-clamp and Western-blot experiments revealed that long-term depolarization brings about a drastic reduction in the amplitude of currents flowing through Cav1.1 channels and in the levels of the α1s subunit, the main subunit of muscle L-type channels. The decline of both phenomena was prevented by the action of the protease inhibitors E64 (50 μM) and leupeptin (50 μM). In contrast, long-term depolarization had no effect on β1, the auxiliary subunit of α1s. The levels of mRNAs coding the α1s and the β1 subunits were measured by RNase protection assays. Neither the content of the α1s nor the β1 subunit mRNAs were affected by long-term depolarization, indicating that the synthesis of Cav1.1 channels remained unaffected. Taken together, our experiments suggest that the reduction in the amplitude of membrane currents and in the α1s subunit levels is caused by increased degradation of this subunit by a Ca2+-dependent protease.

Journal

The Journal of Membrane BiologySpringer Journals

Published: Jan 1, 2004

References

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