Effects of calcitonin gene-related peptide on membrane currents in mammalian cardiac myocytes

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Abstract
We examined the effects of calcitonin gene-related peptide (CGRP) on the membrane currents of single atrial and ventricular cells of guinea pig heart. The tightseal whole-cell voltage-clamp technique was used. In atrial cells, like isoproterenol, CGRP increased the L-type Ca channel current (I Ca.L) in a concentration-dependent manner. Human CGRP-(8-37), a putative CGRP receptor antagonist, completely abolished the CGRP-induced increase of I Ca.L. Although the effects of CRGP were similar to those of isoproterenol, propranolol, a β-adrenergic receptor antagonist, did not affect the CGRP-induced increase of I Ca.L. After I Ca.L had been maximally activated by isoproterenol (2 μM) or intracellular cyclic adenosine 5′-monophosphate (100 μM), CGRP failed to increase I Ca.L. Acetylcholine antagonized the effects of CGRP on I Ca.L. Unlike the effects on atrial cells, CGRP had no significant effects on the membrane currents of ventricular myocytes. Thes results indicate that CGRP increases I Ca.L via adenylate cyclase activation by binding to specific membrane receptors in cardiac atrial myocytes. Furthermore, CGRP receptors are expressed in atrial cells but probably not in ventricular cells.