Long-term depolarization regulates the alpha1s, subunit of skeletal muscle Ca2+ channels and the amplitude of L-type Ca2+ currents.
The effects of long-term depolarization on the level of alpha1s and on L-type Ca2+ currents of skeletal muscle were investigated. Long-term depolarization (14 h) caused a 50% decrease of alpha1s, revealed with the Western blot technique. This decline was prevented by preincubation with the Ca2+ channel blocker nifedipine. Electrophysiological experiments using the voltage-clamp technique were performed to measure the actions of long-term depolarization on Ca2+ currents and charge movement. A progressive decline in the amplitude of the Ca2+ currents by depolarizations lasting 0.5-14 h was observed. Similar to Western blot results, the fall in current amplitude was prevented by nifedipine, and it depended on external Ca2+. The nonlinear charge mobilized by step pulses was also significantly reduced (50%) by long-term depolarization. It is suggested that alpha1s subunit is down-regulated by long-term depolarization by a very stringent mechanism and that, in this process, Ca2+ ions permeating through L-type channels play a key role. A new role for the L-type Ca2+ current in skeletal muscle fibers in which the channels are self-regulated is proposed.
Escamilla
J
J
Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del IPN, Mexico DF, Mexico.
Farías
J M
JM
García
R
R
García
M C
MC
Sánchez
J A
JA
D000814:Aniline Compounds; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D004553:Electric Conductivity; D004594:Electrophysiology; D005456:Fluorescent Dyes; D007700:Kinetics; D008564:Membrane Potentials; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011898:Ranidae; D013050:Spectrometry, Fluorescence; D014966:Xanthenes
D000814:Aniline Compounds; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D005456:Fluorescent Dyes; D014966:Xanthenes; C059715:Fluo-3; D009543:Nifedipine; D002118:Calcium