ATP-SENSITIVE K CHANNEL IS NOT INVOLVED IN THEEXTRACELLULAR K ACCUMULATION IN ISCHEMICMOUSE HEART

摘要

Using mice with homozygous knockout of Kir6.2 gene (a pore-forming subunit of cardiac Katp channel), we investigated the potential contribution of K_(ATP) channels to the extracellular K+ accumulation and electrophysiological alterations during myocardial ischemia. Coronary-perfused mouse left ventricular muscles (stimulated at 5 Hz) were subjected to no-flow ischemia. Transmembrane potential and extracellular K+ concentration ([K+]_0) were measured by using conventional and K+-selective microelectrodes, respectively. In wild-type (WT) hearts, action potential duration at 90% repolarization (APD_(90)) was significantly decreased by 70.l+-5.2% after 10 min of ischemia (P<0.05). Such ischemia-induced shortening of APD_(90) did not occur in Kir6.2-deficient (Kir6.2 KO) hearts. Resting membrane potential in both WT and Kir6.2 KO hearts similarly decreased by 16.8+-5.6 mV (P<0.05) and 15.0+-1.7 mV (P<0.05), respectively. The [K+]_0 in WT hearts increased within the first 5 min of ishemia by 6.9+-2.5 mM (P<0.05) and then reached a plateau. The extracellular K+ accumulation similarly occurred in Kir6.2 KO hearts and degree of [K+]_o was comparable to that in WT hearts (by 7.0+-1.7 mM, P<0.05). Our study provides evidence that the activation of Katp channels contributes to the shortening of APD, whereas K+ efflux through the K_(ATP) channels is not involved in the extracellular K+ accumulation during ischemia.