Excessive repolarization-dependent calcium currents induced by strong depolarizations in rat skeletal myoballs.
1. Whole-cell patch-clamp recordings were used to study voltage-dependent Ca2+ currents in skeletal myoballs cultured from newborn rats. 2. Depolarizing voltage pulses evoked classical L-type Ca2+ currents, whereas repolarization induced tail currents, whose properties deviated from the expected behaviour of the preceding Ca2+ currents in both voltage dependence and kinetics. 3. Depolarizations of up to +10 mV primarily recruited tail currents that correspond to the Ca2+ channels activated and conducting during the depolarizing pulse, but stronger depolarizations yielded an additional tail current component that exceeded the 'normal' tail current amplitude by several-fold. 4. Activation kinetics of the tail currents were biexponential, with a fast time constant matching the activation time course of the pulse currents (tau approximately 40 ms) and an additional slower component with a voltage-dependent time course that had no kinetic counterpart in the pulse currents (tau approximately 150-600 ms). 5. Both pulse and tail currents were blocked by the dihydropyridine, PN200-110, suggesting that they represent Ca2+ channels of the L-type. 6. We suggest the presence of at least two subsets of dihydropyridine-sensitive Ca2+ channels in skeletal muscle cells. One subset has classical L-type channel characteristics and the other has anomalous gating behaviour that is 'activated' or 'primed' by strong and long-lasting depolarizations without conducting significant Ca2+ current--however, upon repolarization, this subset of channels generates large tail currents.
Fleig
A
A
Department of Membrane Biophysics, Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany.
Penner
R
R
D000818:Animals; D000831:Animals, Newborn; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats
D015220:Calcium Channels; D004095:Dihydropyridines