Korean J Physiol Pharmacol.  1997 Dec;1(6):741-748.

Effect of metabolic inhibition on inward rectifier K current in single rabbit ventricular myocytes

Affiliations
  • 1Department of Physiology, Seoul National University, College of Medicine, 28 Yonkeun-Dong, Chongno-Ku, Seoul 110-799, South Korea.

Abstract

In the present study, we have investigated the effect of metabolic inhibition on the inward rectifer K current (IK1). Using whole cell patch clamp technique we applied voltage ramp from +80 mV to -140 mV at a holding potential of -30 mV and recorded the whole cell current in single ventricular myocytes isolated from the rabbit heart. The current-voltage relationship showed N-shape (a large inward current and little outward current with a negative slope) which is a characteristic of IK1. Application of 0.2 mM dinitrophenol (DNP, an uncoupler of oxidative phosphorylation as a tool for chemical hypoxia) to the bathing solution with the pipette solution containing 5 mM ATP, produced a gradual increase of outward current followed by a gradual decrease of inward current with little change in the reversal potential (-80 mV). The increase of outward current was reversed by glibenclamide (10 muM), suggesting that it is caused by the activation of KATP. When DNP and glibenclamide were applied at the same time or glibenclamide was pretreated, DNP produced same degree of reduction in the magnitude of the inward current. These results show that metabolic inhibition induces not only the increase of KATP channel but also the decrease of IK1. Perfusing the cell with ATP-free pipette solution induced the changes very similar to those observed using DNP. Long exposure of DNP (30 min) or ATP-free pipette solution produced a marked decrease of both inward and outward current with a significant change in the reversal potential. Above results suggest that the decrease of IK1 may contribute to the depolarization of membrane potential during metabolic inhibition.

Keyword

DNP; Metabolic inhibition; Whole cell patch clamp; Inward rectifier K current; ATP
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