Calcium channel and calcium pump involved in oscillatory hyperpolarizing responses of L‐strain mouse fibroblasts

Abstract

In fibroblastic L cells, spontaneously repeated hyperpolarizing responses (oscillation of membrane potential) and hyperpolarizing responses evoked by electrical stimuli were suppressed by the external application of a K+ channel blocker, nonyltriethylammonium (C9). This hydrophobic TEA [triethylammonium] analog also inhibited the hyperpolarization induced by intracellular Ca2+ injection. Quinine or quinidine, inhibitors of the Ca2+-activated K+ channel of red cells, instantaneously inhibited these hyperpolarizations. These hyperpolarizations are likely to be caused by the operation of Ca2+-sensitive K+ channels. Azide, which inhibits the mitochondrial Ca2+ uptake in fibroblasts, and caffeine, dantrolene Na and oxalate, which affect the microsomal Ca2+ transport, did not exert any effects upon the electrical potential profiles. Ca2+ channel blockers (nifedipine, D 600 [a verapmil analog] and Co2+) suppressed the hyperpolarizing responses but not the hyperpolarizations produced by intracellular Ca2+ injection, suggesting that the Ca2+ responsible for the hyperpolarizing responses are mainly derived from outside the cell through Ca2+ channels. Flavones of plant origin, which inhibit Ca2+-ATPase, prolonged the duration of the hyperpolarizing phase of the oscillation or produced a sustained hyperpolarization. The Ca2+ channel and the Ca2+ pump play essential roles in the generation of the hyperpolarizing response and of the membrane potential oscillation in L cells. These hyperpolarizations are brought about by a transient elevation of cytosolic Ca2+ level which, in turn, activates Ca2+-dependent K+ channels.