Long-term depolarization regulates the α_1s subunit of skeletal muscle Ca²⁺ channels and the amplitude of L-type Ca²⁺ currents

The effects of long-term depolarization on the level of α_1s and on L-type Ca²⁺ currents of skeletal muscle were investigated. Long-term depolarization (14 h) caused a 50% decrease of α_1s, 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 α_1s 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.