Sarcolemmal K ATP channel triggers delayed ischemic preconditioning in rats

• Published in: American journal of physiology. Heart and circulatory physiology 2005-01, Vol.288 (1), p.H445-H447
• Main Authors: Patel, Hemal H., Gross, Eric R., Peart, Jason N., Hsu, Anna K., Gross, Garrett J.
• Format: Article
• Language: English
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00031.2004

Previous work from our laboratory has shown that the sarcolemmal K ATP channel (sK ATP ) is required as a trigger for delayed cardioprotection upon exogenous opioid administration. We also established that the mitochondrial K ATP (mK ATP ) channel is not required for triggering delayed δ-opioid-induced infarct size reduction. Because mechanistic differences have been found among δ-opioids and that due to ischemic preconditioning (IPC), we determined whether the triggering mechanism of delayed IPC-induced infarct size reduction involves either the sK ATP or mK ATP . Male Sprague-Dawley rats received either sham surgery or IPC (3- to 5-min cycles of ischemia and reperfusion) 24 h before being subjected to 30 min of ischemia and 2 h of reperfusion. Infarct size was determined and expressed as a percentage of the area at risk, with significance compared with sham reported at P ≤ 0.001. A subset of both sham and IPC-treated rats received either the selective sK ATP channel antagonist, HMR-1098 (6 mg/kg), or the selective mK ATP channel antagonist, 5-hydroxydeconoic acid (5-HD; 10 mg/kg), given 5 min before IPC. Rats subjected to IPC demonstrated a significant reduction in infarct size compared with sham (29.2 ± 4.7 vs. 59.3 ± 2.5%, respectively; P ≤ 0.001). Prior administration of HMR-1098, but not 5-HD, abolished IPC-induced infarct size reduction (48.8 ± 2.9 and 28.8 ± 4.0%, respectively; P ≤ 0.001). Furthermore, administration of HMR 24 h after IPC, before index ischemia, did not abrogate IPC-induced infarct size reduction (33.0 ± 5.0 vs. 29.2 ± 4.7%, respectively; P ≤ 0.001). These data suggest that the sK ATP channel is required as a trigger but not a mediator for delayed IPC-induced infarct size reduction in rat hearts.