INDEPENDENT REGULATION OF ACTIVATION AND INACTIVATION PHASES IN NONCONTRACTILE CA2-JUNCTION( TRANSIENTS BY NICOTINIC RECEPTOR AT THE MOUSE NEUROMUSCULAR)

Non-contractile Ca2+ mobilization (not accompanied by muscle contracti on) occurs by the prolonged activation of nicotinic acetylcholine rece ptor in mouse diaphragm muscles treated with anticholinesterase. To el ucidate the regulation properties of non-contractile Ca2+ mobilization by nicotinic receptor, the modes of action of competitive and depolar izing neuromuscular blockers were investigated. (+)-Tubocurarine (0.07 -0.1 mu M), pancuronium (0.05 mu M) and a-bungarotoxin (0.03-0.06 mu M ) decreased decay time (T-2, duration of inactivation phase) without c hanges in rise time (T-1, duration of activation phase) of non-contrac tile Ca2+ transients. These competitive antagonists also suppressed th eir peak amplitude at higher concentrations than those affecting T-2. Contractile Ca2+ transients were not inhibited by these antagonists at the concentrations used. Decamethonium (1 mu M), a depolarizing block er, suppressed the peak amplitude of non-contractile Ca2+ transients w ithout affecting their duration. In contrast, succinylcholine (0.3 mu M) suppressed both peak amplitude and T-1 without changing T-2, presum ably via the receptor desensitization. Succinylcholine but not decamet honium inhibited contractile Ca2+ transients at the concentrations use d. These results demonstrate that the activation and inactivation phas es in non-contractile Ca2+ transients are independently regulated by n icotinic acetylcholine receptor.