[Intracellular calcium ion mobilization and nicotinic acetylcholine receptor-mediated signal transduction in neuro-skeletal muscle synapse].
Intracellular Ca2+ mobilization in neuro-skeletal muscle synapse was studied by measuring Ca2(+)-aequorin luminescence transients (Ca2+ transients). Ca2+ transients were categorized into three groups as follows: (1) The 1st phase of rapid Ca2+ mobilization was accompanied with twitch tension, (2) the 2nd phase of slow Ca2+ mobilization was not accompanied with twitch tension, and only observed in the presence of cholinesterase inhibitors, and (3) the 3rd phase was spontaneous Ca2+ mobilization which was rather related to contracture. The caffeine effects were composed of 1st phase-potentiation (cyclic AMP increase?), 2nd phase-inhibition (n-acetylcholine receptor (AChR) closely related), and the increase of 3rd phase (Ca2+ release from salcoplasmic reticulum). d-Tubocurarine showed much higher potency for the inhibition of the 2nd phase than for that of the 1st phase. These results suggest that the 1st phase Ca2+ transients are related to T-type n-AChR channel, whereas the 2nd phase Ca2+ transients are related to S-type n-AChR channel and its mediated signal transduction.
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical & Pharmaceutical University, Japan.
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Kimura
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism / Q000502:physiology*
D009466:Neuromuscular Blocking Agents; D009467:Neuromuscular Depolarizing Agents; D011978:Receptors, Nicotinic; D002110:Caffeine; D002118:Calcium