title: Sarcolemmal KATP channel triggers delayed ischemic preconditioning in rats.
abstract: 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 delta-opioid-induced infarct size reduction. Because mechanistic differences have been found among delta-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.
authors.affiliation: Medical College of Wisconsin, Department of Pharmacology and Toxicology, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA.
authors.forename: Hemal H
authors.initials: HH
authors.lastname: Patel
authors.forename: Eric R
authors.initials: ER
authors.lastname: Gross
authors.forename: Jason N
authors.initials: JN
authors.lastname: Peart
authors.forename: Anna K
authors.initials: AK
authors.lastname: Hsu
authors.forename: Garrett J
authors.initials: GJ
authors.lastname: Gross
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D003652:Decanoic Acids / Q000494:pharmacology; D006439:Hemodynamics; D006880:Hydroxy Acids / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D009203:Myocardial Infarction / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000378:metabolism*; D013997:Time Factors
chemical_list: D001549:Benzamides; D003652:Decanoic Acids; D006880:Hydroxy Acids; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate; C410297:HMR 1098