Akao M, Otani H, Horie M, Takano M, Kuniyasu A, Nakayama H, Kouchi I, Murakami T, Sasayama S
Cardiovascular Division of Internal Medicine, Kyoto University Hospital, Kyoto 606, Japan.
J Clin Invest. 1997 Dec 15;100(12):3053-9. doi: 10.1172/JCI119860.
The cardiac ATP-sensitive potassium (KATP) 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 ischemic injury. We examined the transcriptional expression of these genes in rats with myocardial ischemia. 60 min of myocardial regional ischemia followed by 24-72 h, but not 3-6 h, of reperfusion specifically upregulated Kir6.1 mRNA not only in the ischemic (approximately 2.7-3.1-fold) but also in the nonischemic (approximately 2.0-2.6-fold) region of the left ventricle. 24 h of continuous ischemia without reperfusion also induced an increase in Kir6.1 mRNA in both regions, whereas 15-30 min of ischemia followed by 24 h of reperfusion did not induce such expression. In contrast, mRNAs for Kir6.2 and SUR2 remained unchanged under these ischemic procedures. Western blotting demonstrated similar increases in the Kir6.1 protein level both in the ischemic (2.4-fold) and the nonischemic (2.2-fold) region of rat hearts subjected to 60 min of ischemia followed by 24 h of reperfusion. Thus, prolonged myocardial ischemia rather than reperfusion induces delayed and differential regulation of cardiac KATP channel gene expression.
心脏ATP敏感性钾（KATP）通道被认为是一种由内向整流钾通道（Kir6.1和/或Kir6.2）亚基和磺脲类受体（SUR2）组成的复合体。该通道在心肌缺血时被激活，保护心脏免受缺血损伤。我们检测了这些基因在心肌缺血大鼠中的转录表达。心肌局部缺血60分钟，随后再灌注24 - 72小时（而非3 - 6小时），不仅使左心室缺血区域（约2.7 - 3.1倍），也使非缺血区域（约2.0 - 2.6倍）的Kir6.1 mRNA特异性上调。持续缺血24小时而无再灌注也使两个区域的Kir6.1 mRNA增加，而缺血15 - 30分钟后再灌注24小时并未诱导这种表达。相比之下，在这些缺血过程中，Kir6.2和SUR2的mRNA保持不变。蛋白质印迹法显示，在经历60分钟缺血后再灌注24小时的大鼠心脏中，缺血区域（2.4倍）和非缺血区域（2.2倍）的Kir6.1蛋白水平均有类似升高。因此，延长的心肌缺血而非再灌注诱导了心脏KATP通道基因表达的延迟和差异调节。
