CONTRIBUTION OF POTASSIUM ACCUMULATION IN NARROW EXTRACELLULAR-SPACES TO THE GENESIS OF NICORANDIL-INDUCED LARGE INWARD TAIL CURRENT IN GUINEA-PIG VENTRICULAR CELLS

The mechanism of nicorandil-induced large inward tail current (I(tail)) in single guinea-pig ventricular cells was investigated using the whole-cell patch-clamp technique. In the presence of 0.5 - 1.0 mM nicorandil., an activator of adenosine 5'-triphosphate (ATP)-sensitive K+ current (I(KATP)), a depolarization pulse causing a large outward current was followed by a large inward I(tail) on the repolarization step to the holding potential at - 85 mV. The larger the outward current, the greater the I(tail). The amplitude of I(tail) increased as a single exponential function (tau = 74.9 ms) as the duration of preceding depolarization was prolonged. Both the outward current and I(tail) were inhibited nearly completely after application of glibenclamide (1 muM), a specific blocker of I(KAPT). Substitution of K+ with Cs+ in both the external and internal solutions resulted in a virtual elimination of I(tail). I(tail) was well preserved under the condition where Ca2+ entry during the preceding depolarization was largely inhibited or where external Na+ was replaced by Li+. A transient positive shift of reversal potential for the net current was observed at the peak of I(tail). At 30 mM external K+ concentration, I(tail) was almost eliminated. From these findings, it is concluded that the I(tail) is a K+ current associated with an alteration of the K+ equilibrium potential (E(K)) following a substantial K+ efflux. This E(K) change is most likely explained by an accumulation of K+ in transverse tubules (T-tubules) since I(tail) was not induced in atrial cells in which T-tubules are poorly developed.