Noncontractile acetylcholine receptor-operated Ca++ mobilization: suppression of activation by open channel blockers and acceleration of desensitization by closed channel blockers in mouse diaphragm muscle.

The effects of various blockers of the nicotinic acetylcholine receptor-activated ionic channel on noncontractile slow Ca++ mobilization were investigated at the neuromuscular synapse of aequorin-injected diaphragm muscles of mice. Intracellular Ca++ mobilization (Ca++ transients) was evoked in the presence of neostigmine (0.3 microM) by nerve stimulation. Bupivacaine, an open channel blocker, decreased the peak amplitude, whereas chlorpromazine, a closed channel blocker, shortened the duration. Phencyclidine, an open and closed channel blocker, decreased both peak amplitude and duration. beta-Eudesmol, a compound of Atractylodes lancea, clearly and specifically shortened the duration but had little effect on peak amplitude. All the above channel blockers, when given in the same concentration ranges, also blocked the total amount of contractile Ca++ transients. The effects of bupivacaine, chlorpromazine and phencyclidine on noncontractile Ca++ transients were not affected by 5 mM [Ca++]o, whereas the effect of beta-eudesmol was enhanced. Geographutoxin II (0.3 microM), a skeletal muscle Na+ channel blocker, selectively and partly reversibly blocked contractile Ca++ transients without affecting noncontractile ones. These results suggest that: 1) the activation of noncontractile Ca++ mobilization is suppressed by open channel blockers, whereas its desensitization is accelerated by closed channel blockers and 2) activation of the muscle Na+ channel and subsequent release of Ca++ from sarcoplasmic reticulum is not involved in the mechanism of noncontractile Ca++ mobilization. It may reflect the steps of the desensitization process.