Effects of calcitonin gene-related peptide on membrane currents in mammalian cardiac myocytes.
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 tight-seal whole-cell voltage-clamp technique was used. In atrial cells, like isoproterenol, CGRP increased the L-type Ca channel current (ICa.L) in a concentration-dependent manner. Human CGRP-(8-37), a putative CGRP receptor antagonist, completely abolished the CGRP-induced increase of ICa.L. Although the effects of CGRP were similar to those of isoproterenol, propranolol, a beta-adrenergic receptor antagonist, did not affect the CGRP-induced increase of ICa.L. After ICa.L had been maximally activated by isoproterenol (2 microM) or intracellular cyclic adenosine 5'-monophosphate (100 microM), CGRP failed to increase ICa.L. Acetylcholine antagonized the effects of CGRP on ICa.L. Unlike the effects on atrial cells, CGRP had no significant effects on the membrane currents of ventricular myocytes. These results indicate that CGRP increases ICa.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.
Nakajima
T
T
2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Takikawa
R
R
Sugimoto
T
T
Kurachi
Y
Y
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials; D009206:Myocardium / Q000166:cytology; D010446:Peptide Fragments / Q000494:pharmacology
D015220:Calcium Channels; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine