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. 1. 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 tauinactivation and taurecovery. This indicates that acidosis exerts a complex effect on the slow membrane channel. 2. The normal response of the Ca current towards variations of the extracellular Ca concentration (0.5-4 mM) or towards the addition of the beta-stimulating compound isoproterenol (2 mg/l) was not altered by the lowered extracellular pH. 3. 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. 4. At pH 5.5 excess Ca (4 mM) 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 beta-stimulating compound remained unchanged.

The effect of extracellular low pH on the plateau current in isolated, single rat ventricular cells - A voltage clamp study.

“…In the frog atrial muscle, low pH decreases both IS and the outward current (CHESNAIS et al, 1975;WADA and GoTo, 1975). Our results are similar to those of KoHLHARDT et al (1976), however they found no shift of the I-V curve when the external pH was changed from 7.4 to 5.5, while in our experiments, I -V curve shifted to a less negative voltage. A genuine species difference, or unknown differences in experimental technique may be involved in the discrepancy.…”

“…With respect to earlier observations in the cat papillary muscle, it has been reported that reduction of external pH reduces the slow inward current and increases the time constant of inactivation (KoHLHARDT et al, 1976). In the frog atrial muscle, low pH decreases both IS and the outward current (CHESNAIS et al, 1975;WADA and GoTo, 1975).…”

“…Electrophysiological effects of H+ on the myocardium are of clinical importance, as there are considerable variations in the level of H+ during myocardial ischemia, and the effect of lowering external pH on the membrane potential and currents has been reported (CHESNAIS et al, 1975;WADA and GoTo, 1975;KOHLHARDT et a!.,1976; but it has to current passing through a microelectrode. The voltage is measured only when the discontinuous or chopped current is zero, yielding an accurate measurement of membrane potential.…”

Effects of acid-base imbalance on vascular reactivity

“…Perivascular pH can affect many cellular processes (4), but the precise mechanisms of vascular hyporesponsiveness remain uncertain. Low pH has been shown to reduce Ca 2+ influx (37), to inhibit myofilament contractility (38) and to alter receptors on the cell surface (39), accounting for the attenuation of vasoconstrictor responses.…”

Hydrogen ion modulation of Ca channel current in cardiac ventricular cells. Evidence for multiple mechanisms.

“…One such perturbation is extracellular acidosis, which can occur during myocardial ischemia. Chesnais et al (1975), Kohlhardt et al (1976), and Yatani and Goto (1983) have all shown that acidosis depresses Ca channel current and, therefore, overall cardiac performance.…”