MYOCARDIAL-ISCHEMIA INDUCES DIFFERENTIAL REGULATION OF K-ATP CHANNEL GENE-EXPRESSION IN RAT HEARTS

The cardiac ATP-sensitive potassium (K-ATP) channel is thought to be a complex composed of an inward rectifier potassium channel (Kir6.1 and /or Kir6.2) subunit and the sulfonylurea receptor (SUR2), This channel is activated during myocardial ischemia and protects the heart from i schemic injury. We examined the transcriptional expression of these ge nes in rats with myocardial ischemia, 60 min of myocardial regional is chemia followed by 24-72 h, but not 3-6 h, of reperfusion specifically upregulated Kir6.1 mRNA not only in the ischemic (similar to 2.7-3.1- fold) but also in the nonischemic (similar to 2.0-2.6-fold) region of the left ventricle. 24 h of continuous ischemia without reperfusion al so induced an increase in Kir6.1 mRNA in both regions, whereas 15-30 m in of ischemia followed by 24 h of reperfusion did not induce such exp ression. In contrast, mRNAs for Kir6.2 and SUR2 remained unchanged und er these ischemic procedures. Western blotting demonstrated similar in creases in the Kir6.1 protein level both in the ischemic (2.4-fold) an d the nonischemic (2.2-fold) region of rat hearts subjected to 60 min of ischemia followed by 24 h of reperfusion. Thus, prolonged myocardia l ischemia rather than reperfusion induces delayed and differential re gulation of cardiac K-ATP channel gene expression.