Restoration by histamine of the calcium-dependent electrical and mechanical response in the guinea-pig papillary muscle partially depolarized by potassium

Abstract

Electrophysiological and mechanical effects of histamine were observed in guinea-pig papillary muscle which had been depolarized and rendered inexcitable by elevation of potassium concentration in Tyrode solution to 27 mM. 1. Histamine (3 X 10(-7) to 3 X 10(-5) M) restored the action potential and tension development. The amplitude of the action potential was increased by 31.6 mV/10-fold increase in extracellular Ca2+ concentration. Nifedipine (10(-6) M) abolished the electrical and mechanical responses which had been restored by histamine (10(-5) M) but TTX (10(-5) M) did not affect them. Reduction of the extracellular Na+ concentration to one half decreased the amplitude and the maximum rate of rise of the action potential restored by histamine (10(-5) M) while the peak tension was increased and an after-contraction occurred. 2. The maximum rate of rise and the amplitude of the action potential restored by histamine (10(-5) M) decreased with increase in stimulus frequency from 0.1-1.6 Hz. The peak tension decreased and then increased. The shape of the developed tension was also changed. In the presence of caffeine (1 mM), the only effect of an increase in stimulus frequency was a decrease in peak tension but the change in the shape of developed tension did not occur. 3. The electrical and mechanical responses restored by histamine (3 X 10(-6) or 10(-5) M) were depressed by metiamide (3 X 10(-6) M) but not by diphenhydramine (10(-5) M) or bufetolol (10(-6) M). 4. The electrical response restored by histamine (10(-6) or 10(-5) M) was enhanced by papaverine (10(-5) M) and depressed by N-methylimidazole (10 mM). It is concluded that histamine may enhance the slow inward Ca2+ current mediated by histamine H2-receptors and the adenylate cyclase system in ventricular muscle and that the positive inotropic action of histamine may be attributed to these mechanisms.

Α‐sympathomimetic Amines and Calcium‐mediated Action Potentials in Guinea‐pig Ventricular Muscle

“…We have confirmed that in guinea-pig ventricular strips paced at 0.5 Hz, methoxamine consistently caused a dose-dependent positive inotropic effect ( Figure 6) Eibach, 1976;Inui & Imamura, 1976); the restoration of excitability and contractility in these preparations can be taken to indicate that the drugs increase calcium influx.…”

Histamine induced or enhanced delayed afterdepolarization and triggered activity in guinea-pig papillary muscles. A preliminary study.

“…These effects of histamine through the histamine H2 receptors in the ventricular muscles were consistent with previous studies utilizing laboratory animals.13)- 16) It has already been suggested6),7) that histamine might produce its positive inotropic and phosphorylase activating effects by increasing cardiac cyclic AMP in a manner analogous to that proposed for norepinephrine. We investigated the effects of a PDE inhibitor, papaverine, and an activator, Nmethylimidazole, on the histamine induced DAD to study the participation of increased cyclic AMP in the induction of DAD; the former and the latter enhanced and suppressed the DAD amplitude, which is circumstantial evidence for a role of increased cyclic AMP.…”

The arrhythmogenic actions of histamine on human atrial fibers.

“…The positive chronotropic effect of histamine has been explained on the basis of an increase in slow inward Ca 2+ current (Houki, 1973;Inui and Imamura, 1976;Ledda et al, 1976;Levi and Pappano, 1978). The induction by histamine of delayed afterdepolarizations and triggered activity, and their abolition by the slow channel blocker verapamil (see , are consistent with the hypothesis that histamine acts by enhancing slow inward (presumably Ca 2+ ) current.…”