Independent regulation of activation and inactivation phases in non-contractile Ca2+ transients by nicotinic receptor at the mouse neuromuscular junction.
Non-contractile Ca2+ mobilization (not accompanied by muscle contraction) occurs by the prolonged activation of nicotinic acetylcholine receptor in mouse diaphragm muscles treated with anticholinesterase. To elucidate the regulation properties of non-contractile Ca2+ mobilization by nicotinic receptor, the modes of action of competitive and depolarizing neuromuscular blockers were investigated. (+)-Tubocurarine (0.07-0.1 microM), pancuronium (0.05 microM) and alpha-bungarotoxin (0.03-0.06 microM) decreased decay time (T2, duration of inactivation phase) without changes in rise time (T1, duration of activation phase) of non-contractile Ca2+ transients. These competitive antagonists also suppressed their peak amplitude at higher concentrations than those affecting T2. Contractile Ca2+ transients were not inhibited by these antagonists at the concentrations used. Decamethonium (1 microM), a depolarizing blocker, suppressed the peak amplitude of non-contractile Ca2+ transients without affecting their duration. In contrast, succinylcholine (0.3 microM) suppressed both peak amplitude and T1 without changing T2, presumably via the receptor desensitization. Succinylcholine but not decamethonium inhibited contractile Ca2+ transients at the concentrations used. These results demonstrate that the activation and inactivation phases in non-contractile Ca2+ transients are independently regulated by nicotinic acetylcholine receptor.
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
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Tsuneki
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Kimura
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Kimura
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D003964:Diaphragm / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009119:Muscle Contraction / Q000187:drug effects; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects*; D018733:Nicotinic Antagonists; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009466:Neuromuscular Blocking Agents; D018733:Nicotinic Antagonists; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic