Calcitonin gene‐related peptide potentiates nicotinic acetylcholine receptor‐operated slow Ca 2+ mobilization at mouse muscle endplates

1 The involvement of calcitonin gene‐related peptide (CGRP) in the non‐contractile slow Ca 2+ mobilization induced by prolonged nicotinic stimulation was investigated by measurement of [Ca 2+ ] i levels in mouse single muscle cells (flexor digitorum brevis; FDB) loaded with a Ca 2+ indicator fluo‐3 using confocal laser scanning microscopy. 2 CGRP (3–30 n M ) potentiated acetylcholine (ACh, 1 μ M )‐elicited slow Ca 2+ mobilization in a concentration‐dependent manner. 3 The potentiation by CGRP of the slow Ca 2+ component was greatly depressed by a competitive nicotinic antagonist (+)‐tubocurarine (5 μ M ). The Ca 2+ channel blocker nitrendipine (1 μ M ) affected neither ACh responses nor the CGRP potentiation. 4 The slow Ca 2+ component was completely abolished by reducing [Ca 2+ ] 0 from 2.5 to 0.25 m M whereas the fast component was not affected. The CGRP‐induced potentiation of slow Ca 2+ signal was also depressed by decreasing [Ca 2+ ] 0 . 5 Isoproterenol (30 μ M ) and 8‐bromo‐adenosine 3′,5′‐cyclic monophosphate (1 m M ) potentiated the ACh‐elicited slow Ca 2+ response. The potentiation by CGRP of the slow Ca 2+ component was completely abolished by a protein kinase‐A inhibitor H‐89 (1 μ M ). 6 These findings indicate that CGRP potentiates the nicotinic ACh receptor‐operated slow Ca 2+ signal via the activation of protein kinase‐A system at the skeletal muscle endplates.British Journal of Pharmacology (1998) 125 , 277–282; doi: 10.1038/sj.bjp.0702058