Electrophysiological and mechanical effects of calcitonin gene-related peptide on guinea-pig atria.
1. The effects of calcitonin gene-related peptide (CGRP) on mechanical and electrophysiological responses were studied in the guinea-pig atrial muscle preparations and in single cells. 2. CGRP (greater than 10(-9) M) enhanced the twitch contraction in a concentration-dependent manner in electrically driven left atria and increased heart rate in spontaneously beating right atria. The positive inotropic and chronotropic effects of CGRP were not inhibited by propranolol but were attenuated by reduction of the calcium concentration in the bathing medium. 3. In single left atrial cells, CGRP slightly hyperpolarized the resting potential but did not affect the other action potential parameters significantly. 4. Under whole-cell voltage-clamp conditions, CGRP increased the calcium inward current. The peptide also increased the steady inward current elicited by hyperpolarization and the late outward current by depolarization. 5. These results suggest that CGRP may produce the positive inotropic and presumably chronotropic effects by increasing calcium inward current. CGRP also increases the potassium permeability. Such effects on ionic currents may not produce any apparent change in the action potential conformation, due to their opposite directional actions and relatively weak potencies.
Department of Pharmacology, Fukui Medical School, Japan.
T
T
Ohmura
M
M
Nishio
S
S
Kigoshi
I
I
Muramatsu
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D011433:Propranolol / Q000494:pharmacology
D007473:Ion Channels; D011433:Propranolol; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium