1. Regenerative Ca2+ waves and oscillations indicative of calcium-induced c
alcium release (CICR) activity were induced in fully polarized, fluo-3-load
ed, intact frog skeletal muscle fibres by exposure to hypertonic Ringer sol
utions.
2. The calcium waves persisted in fibres exposed to EGTA-containing solutio
ns, 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 r
yanodine and tetracaine, and potentiated by caffeine.
4. In addition to these pharmacological properties, the amplitudes, frequen
cy and velocity of such hypertonicity-induced waves closely resembled those
of Ca2+ waves previously described in dyspedic skeletal myocytes expressin
g the cardiac RyR-2.
5. Quantitative transmission and freeze-fracture electronmicroscopy demonst
rated a reversible cell shrinkage, transverse (T)-tubular luminal swelling
and decreased T-sarcoplasmic reticular (SR) junctional gaps in fibres maint
ained 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 op
erate even in such fully polarized skeletal muscle fibres.