Electrophysiological and mechanical effects of calcitonin gene‐related peptide on guinea‐pig atria

Abstract

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 (>10-9M) 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.

Electrophysiological effects of calcitonin gene‐related peptide in bull‐frog and guinea‐pig atrial myocytes.

“…However, ICa and 'K appeared to be about equally sensitive to CGRP at this temperature (data not shown), and the marked prolongation of the action potential duration was still observed (Ishikawa et al 1988). Recently, Ohmura, Nishio, Kigoshi & Muramatsu (1990) have reported somewhat similar results, i.e. CGRP increased both ICa and IK to a similar extent at 33°C.…”

Calcitonin gene-related peptide and its receptors: molecular genetics, physiology, pathophysiology, and therapeutic potentials

“…A positive inotropic effect in the atrium, however, is thought to be produced by cAMP-mediated stimulation of delayed-rectifier potassium currents (365-367). Positive chronotropic and inotropic effects of CGRP in the atrium are mediated through the CGRP a receptor subtype, as these effects are antagonized by CGRP 8 _3 7 (277,(410)(411)(412)(413).…”

Calcitonin gene-related peptide suppresses the transient outward current in rat ventricular myocytes

“…This corresponds well with the study of Bell and McDermott [6] who have demonstrated that the positive inotropic effect of CGRP in rat ventricular myocytes is not antagonized by the selective L-type Ca 2+ channel antagonists, diltiazem or verapamil. On the other hand, in preparations such as guinea-pig atrial myocytes, CGRP stimulates cAMP production and I Ca,L [16,23,24]. Increased cAMP levels in the presence of CGRP have been reported also in cultured neonatal rat myocardial cells [22] and in rat atria [15,29] but not in ventricles [15].…”

“…With regard to the inotropic effects conflicting results have been reported depending on the animal species and tissue studied. The positive inotropic effect in guinea-pig atrial myocytes has been attributed to the stimulation of Ca 2+ currents and adenosine 3′,5′-cyclic monophosphate (cAMP) production [16,23,24]. In rat ventricular cells a positive inotropic effect is also found, although it is insensitive to selective blockers of L-type Ca 2+ channels as well as to a cAMP antagonist [4,5,6].…”