Abstract
1. Regenerative Ca2+ waves and oscillations indicative of calcium-induced calcium release (CICR) activity were induced in fully polarized, fluo-3-loaded, intact frog skeletal muscle fibres by exposure to hypertonic Ringer solutions. 2. The calcium waves persisted in fibres exposed to EGTA-containing solutions, during sustained depolarization of the membrane potential or following treatment with the dihydropyridine receptor (DHPR)-blocker nifedipine. 3. The waves were blocked by the ryanodine receptor (RyR)-specific agents ryanodine and tetracaine, and potentiated by caffeine. 4. In addition to these pharmacological properties, the amplitudes, frequency and velocity of such hypertonicity-induced waves closely resembled those of Ca2+ waves previously described in dyspedic skeletal myocytes expressing the cardiac RyR-2. 5. Quantitative transmission and freeze-fracture electronmicroscopy demonstrated a reversible cell shrinkage, transverse (T)-tubular luminal swelling and decreased T-sarcoplasmic reticular (SR) junctional gaps in fibres maintained in and then fixed using hypertonic solutions. 6. The findings are consistent with a hypothesis in which RyR-Ca2+ release channels can be partially liberated from their normal control by T-tubular DHPR-voltage sensors in hypertonic solutions, thereby permitting CICR to operate even in such fully polarized skeletal muscle fibres.
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