Forskolin, a new positive inotropic agent, and its influence on myocardial electrogenic cation movements.

Abstract:

:Forskolin exerts concentration-dependent positive inotropic effects in guinea pig isolated papillary muscles; resting potential, overshoot, and upstroke velocity remain unchanged. It markedly potentiates Ca2+-mediated action potentials elicited in partially depolarized myocardial fibers (increases in upstroke velocity, height, and action potential duration) and restores slow-channel-mediated transmembrane Ca2+ influx and contractile force under conditions of external Ca2+ withdrawal or in the presence of the specific Ca2+ antagonist D 600. In partially depolarized ventricular muscle, the potentiation of transmembrane inward Ca2+ current by forskolin is correlated with a reciprocal inhibition of Mg2+-induced electrogenic membrane effects. In this respect, forskolin resembles other Ca2+ influx promoters such as beta-adrenoceptor agonists, histamine, and dibutyryl-cyclic AMP (cAMP). All these agents favor sarcolemmal Ca2+ accumulation through increases in intracellular cAMP and the subsequent formation of Ca2+-binding phosphorylated membrane proteins; Mg2+ ions seem to be displaced by Ca2+. These findings support the concept that the effects of forskolin result from an increase in intracellular cAMP.

journal_name

J Cardiovasc Pharmacol

authors

Späh F

subject

Has Abstract

pub_date

1984-01-01 00:00:00

pages

99-106

issue

1

eissn

0160-2446

issn

1533-4023

journal_volume

6

pub_type

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