Sustained release of calcium elicited by membrane depolarization in ryanodine-injected mouse skeletal muscle fibers.
The effect of micromolar intracellular levels of ryanodine was tested on the myoplasmic free calcium concentration ([Ca(2+)](i)) measured from a portion of isolated mouse skeletal muscle fibers voltage-clamped at -80 mV. When ryanodine-injected fibers were transiently depolarized to 0 mV, the early decay phase of [Ca(2+)](i) upon membrane repolarization was followed by a steady elevated [Ca(2+)](i) level. This effect could be qualitatively well simulated, assuming that ryanodine binds to release channels that open during depolarization and that ryanodine-bound channels do not close upon repolarization. The amplitude of the postpulse [Ca(2+)](i) elevation depended on the duration of the depolarization, being hardly detectable for pulses shorter than 100 ms, and very prominent for duration pulses of seconds. Within a series of consecutive pulses of the same duration, the effect of ryanodine produced a staircase increase in resting [Ca(2+)](i), the slope of which was approximately twice larger for depolarizations to 0 or +10 mV than to -30 or -20 mV. Overall results are consistent with the "open-locked" state because of ryanodine binding to calcium release channels that open during depolarization. Within the voltage-sensitive range of calcium release, increasing either the amplitude or the duration of the depolarization seems to enhance the fraction of release channels accessible to ryanodine.
Collet
Claude
C
Laboratoire de Physiologie des Eléments Excitables, Université Claude Bernard Lyon 1, F69622 Villeurbanne, France.
Jacquemond
Vincent
V
D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D002118:Calcium / Q000378:metabolism*; D002138:Calibration; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D004594:Electrophysiology; D005456:Fluorescent Dyes / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D008856:Microscopy, Fluorescence; D018482:Muscle, Skeletal / Q000187:drug effects*; D012433:Ryanodine / Q000494:pharmacology*; D013997:Time Factors
D005456:Fluorescent Dyes; D007211:Indoles; D012433:Ryanodine; C048960:indo-1; D002118:Calcium