The effects of ryanodine, EGTA and low‐sodium on action potentials in rat and guinea‐pig ventricular myocytes: evidence for two inward currents during the plateau

Abstract

Action potentials were recorded from single cells isolated from rat and guinea‐pig ventricular muscle. In rat cells the repolarization showed two distinct phases, referred to as the early and late phases. In guinea‐pig cells there was a maintained plateau. Reducing external sodium by replacement with lithium or choline suppressed the late phase of the action potential in rat cells, and shortened the plateau of the action potential in guinea‐pig cells. Intracellular EGTA abolished contraction while suppressing the late phase of the action potential in rat cells, and shortening the plateau in guinea‐pig cells. Ryanodine (1 μm), which is thought to inhibit the release of calcium from internal stores, suppressed contraction and the late phase of the action potential in rat cells. In guinea‐pig cells, there was no substantial effect of ryanodine (1 μm) on either contraction or the time course of the action potential. The late phase of the action potential in rat cells was suppressed by increasing the external potassium concentration to 12 mm, and enhanced by reducing external potassium to 1.2 mm It is concluded that an inward current activated by internal calcium contributes to the late phase of the action potential in rat cells, and to the plateau in guinea‐pig cells. Two possibilities are a current arising from electrogenic sodium‐calcium exchange, and a current through ion channels activated by calcium. The effects of reducing external sodium would be consistent with either mechanism. The contribution of such an inward current would be expected to be modified by outward currents through a rectifying potassium conductance which varies with external potassium concentration. In the rat, but not the guinea‐pig, the rise in internal calcium which activates the inward current seems to be largely dependent on ryanodine‐sensitive release of calcium from internal stores.

Caffeine‐induced decreases in the inward rectifier potassium and the inward calcium currents in rat ventricular myocytes

“…The effect of caffeine on the action potential repolarization is not entirely clear. The lack of calcium release during the action potential greatly diminishes the depolarizing Na-Ca exchanger current, therefore, it should shorten the action potential duration in rat ventricular myocardium as it was reported with ryanodine (Mitchell et al, 1984 The reported data with caffeine on the inward calcium current are conflicting. Yatani et al (1984) found that caffeine increased the inward calcium current in rat single ventricular myocytes, but Eisner et al (1979) observed the opposite effect with caffeine on the inward calcium current in sheep cardiac Purkinje fibres.…”

Strontium, nifedipine and 4‐aminopyridine modify the time course of the action potential in cells from rat ventricular muscle

“…It is possible that ISi in these cells also contributes to the initiation of the action potential plateau and that, although two phases of the action potential plateau are not visible, another inward current is present to maintain the plateau at a depolarized level. This possibility is considered in detail in the accompanying paper (Mitchell et al, 1984). As seen above, in the presence of strontium, rat action potentials themselves may show only one long plateau, thus obscuring two underlying phases (cf.…”

Effects of captopril on membrane current and contraction in single ventricular myocytes from guinea‐pig

“…Cells were isolated from both ventricles of female DunkinHartley guinea-pigs weighing 400-600g by an enzyme technique (Mitchell et al, 1984) and were layered on a glass coverslip which formed the base of a perfusion chamber situated on …”