VOLTAGE-DEPENDENT POTENTIATION OF L-TYPE CA2-DEPENDENT PROTEIN-KINASE( CHANNELS DUE TO PHOSPHORYLATION BY CAMP)

THE force of contraction of motor units in skeletal muscle is graded b y changing the discharge rate of motor neurons1, and cytosolic calcium transients are similarly increased2. During single twitches, contract ion is not dependent on extracellular calcium3, and L-type Ca2+ channe ls may only function as voltage sensors for initiating Ca2+ release fr om the sarcoplasmic reticulum4-6. In contrast, forceful tetanic contra ctions triggered by action potentials at high frequency (20 to 200 Hz) are dependent on extracellular Ca2+ concentration and sensitive to L- type Ca2+ channel antagonists7-9, but the mechanism of regulation of c ontractile force is unknown. Here we report a large, voltage- and freq uency-dependent potentiation of skeletal muscle L-type Ca2+ currents b y trains of high-frequency depolarizing prepulses, which is caused by a shift in the voltage-dependence of channel activation to more negati ve membrane potentials and requires phosphorylation by cyclic AMP-depe ndent protein kinase in a voltage-dependent manner. This potentiation would substantially increase Ca2+ influx and contractile force in skel etal muscle fibres in response to tetanic stimuli.