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. 1993 Oct;110(2):639–644. doi: 10.1111/j.1476-5381.1993.tb13859.x

Enhancement by calcitonin gene-related peptide of nicotinic receptor-operated noncontractile Ca2+ mobilization at the mouse neuromuscular junction.

I Kimura 1, H Tsuneki 1, K Dezaki 1, M Kimura 1
PMCID: PMC2175906  PMID: 8242236

Abstract

1. The involvement of calcitonin gene-related peptide (CGRP) in the mechanism of nicotinic acetylcholine receptor-operated noncontractile Ca2+ mobilization (not accompanied by twitch tension) was investigated by measuring Ca(2+)-aequorin luminescence at the neuromuscular junction of mouse diaphragm muscle treated with neostigmine. 2. Noncontractile Ca2+ transients were enhanced by 4-aminopyridine (100 microM), a K+ channel blocker, and inhibited by botulinum toxin (1-100 micrograms, i.p.) and hexamethonium (10-100 microM), a neuronal nicotinic receptor antagonist. 3. Noncontractile Ca2+ transients were diminished by CGRP8-37 (10-20 microM), a CGRP antagonist. CGRP (0.3-10 nM) prolonged the duration of noncontractile Ca2+ transients. The effect of CGRP was suppressed by CGRP8-37 (0.1 microM). 4. Noncontractile Ca2+ transients were inhibited by H-89 (0.1-1 microM), a protein kinase-A inhibitor. The catalytic subunit of protein kinase-A and AA373 (300 microM), a protein kinase-A activator, prolonged the duration of noncontractile transients. The prolongations either by CGRP or by AA373 were not observed in the presence of H-89 (0.1 microM). 5. Contractile (accompanied by twitch tension) but not noncontractile Ca2+ transients were decreased by 12-O-tetradecanoyl phorbol 13-acetate (TPA, 0.3-1 microM), a protein kinase-C activator. Phospholipase A2 increased only contractile Ca2+ transients. Calmodulin-related agents affected neither type of Ca2+ transients. 6. These results provide the first evidence that nicotinic acetylcholine receptor-operated noncontractile Ca2+ mobilization is promoted by nerve-released CGRP activating protein kinase-A, and is dependent on the accumulated amounts of acetylcholine at the neuromuscular junction where desensitization might readily develop.

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Selected References

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