Voltage-dependent calcium fluxes in skeletal muscle transverse tubule membranes in the range of late afterpotentials

Calcium flux responses mediated by voltage-dependent calcium channels have been studied in transverse tubule membrane vesicles from rabbit skeletal muscle. Vesicles were loaded with 45Ca2+, and membrane potentials were generated by establishing potassium gradients across the membrane in the presence of valinomycin. After the membranes were polarized to an estimated −80 mV to approximate the resting state of the cell, a significant 45Ca2+ efflux occurred upon subsequent depolarization to −60 mV. The efflux response was modulated by activators and inhibitors of slow, dihydropyridine-sensitive calcium channels, being inhibited by inorganic calcium channel blockers, verapamil, nifedipine, and (−)-SDZ 202 – 791 and potentiated by the dihydropyridine agonists (±)-Bay K8644 and (+)-SDZ 202 – 791. These results demonstrate that calcium channels in transverse tubule membranes can open to mediate calcium flux in the same range of membrane potential as the late afterpotentials that occur during tetanic contractions of intact muscle fibres.Key words: Ca2+ channels, dihydropyridines, skeletal muscle (rabbit), 45Ca2+ flux, late afterpotentials.