Influence of low extracellular pH upon the Ca inward current and isometric contractile force in mammalian ventricular myocardium

Abstract

In isolated papillary muscles of cats the changes in Ca inward current and isometric contractile force following a decrease of extracellular pH from 7.4 to 5.5 were studied. The Ca current was analyzed (a) by measuring the upstroke velocity of Ca-mediated action potentials and (b) in voltage clamp experiments using the double sucrose gap technique. At a pH of 5.5 the upstroke velocity of the Ca-mediated action potential decreased to 65% of the control, while overshoot and action potential duration remained almost unchanged. Furthermore, the relative refractory period was prolonged and in some cases, a “Wenckebach-like” phenomenon occurred. In voltage clamp experiments, the slow inward current was found to be diminished to 50–60% of the initial control value and over a broad voltage range the current voltage relationship curve was shifted to weaker currents. Acidosis did not influence the steady state inactivation but altered the kinetics of inactivation of the slow inward current and induced an increase of τ_inactivation and τ_recovery. This indicates that acidosis exerts a complex effect on the slow membrane channel. The normal response of the Ca current towards variations of the extracellular Ca concentration (0.5–4 mM) or towards the addition of the β-stimulating compound isoproterenol (2 mg/l) was not altered by the lowered extracellular pH. In the acid medium, isometric contractile force declined to 40% of the control value within 25 min and, thus, reacted stronger than the Ca current. This indicates that those forms of acidosis used in the present experiments caused their negative inotropic effect not exclusively via a depression of the Ca current. Rather an additional intracellular effect has to be assumed which finally leads to a reduced activity of the contractile system. At pH 5.5 excess Ca (4mM) induced the same quantitative response of the contractile system as obtained at normal pH. In contrast, the positive-inotropic effect of 2 mg/l isoproterenol was more pronounced, whilst the sensitivity of the Ca inward current towards this β-stimulating compound remained unchanged.