Abstract
The mechanism of nicorandil-induced large inward tail current (Itail) 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 (IKATP), a depolarization pulse causing a large outward current was followed by a large inward Itail on the repolarization step to the holding potential at -85 mV. The larger the outward current, the greater the Itail. The amplitude of Itail increased as a single exponential function (tau = 74.9 ms) as the duration of preceding depolarization was prolonged. Both the outward current and Itail were inhibited nearly completely after application of glibenclamide (1 microM), a specific blocker of IKATP. Substitution of K+ with Cs+ in both the external and internal solutions resulted in a virtual elimination of Itail. Itail 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 Itail). At 30 mM external K+ concentration, Itail was almost eliminated. From these findings, its is concluded that the Itail is a K+ current associated with an alteration of the K+ equilibrium potential (EK) following a substantial K+ efflux. This EK change is most likely explained by an accumulation of K+ in transverse tubules (T-tubules) since Itail was not induced in atrial cells in which T-tubules are poorly developed.
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