title: ATP-dependent potassium channels involved in the cardiac protection induced by intermittent hypoxia against ischemia/reperfusion injury.
abstract: The aim of this study was to investigate the protection afforded by intermittent hypoxia (IH) against ischemia/reperfusion injury and its effects on calcium homeostasis during ischemia/reperfusion. The roles of KATP channels in these two actions were to be explored. Isolated hearts from IH and normoxic rats were subjected to 30 min global ischemia followed by 30 min reperfusion. Cardiac function was less deteriorated during ischemia and reperfusion in the IH rat hearts compared to normoxia rat hearts. Amplitude of the maximal contracture during ischemia was lower, while time to maximal contracture was extended in IH hearts. Post-ischemic recovery of left ventricular developed pressure and +/-dP/dtmax were higher in IH hearts than in normoxic hearts. KATP antagonist glibenclamide (10 microM) completely abolished these protective effects of IH, but had no appreciable influence on normoxic hearts. In cardiomyocytes isolated from normoxic hearts, [Ca2+]i, measured as arbitrary units of fluorescence ratio (340 nm/380 nm) of fura-2, gradually increased during 20 min simulated ischemia and kept at high level during 30 min reperfusion (1.081 +/- 0.004 and 1.088 +/- 0.006 respectively, p<0.01 vs pre-ischemia perfusion). However, in cardiomyocytes isolated from IH hearts, [Ca2+]i kept at normal level during ischemia and reperfusion (1.012 +/- 0.006 and 1.021 +/- 0.002 respectively, P>0.05 vs pre-ischemia perfusion). 10 microM glibenclamide and 100 microM 5-hydroxydecanoate (a selective mitochondria KATP antagonist) respectively abolished this effect of IH; calcium overloading reappeared during ischemia (1.133 +/- 0.007 and 1.118 +/- 0.007 respectively, P<0.01) and reperfusion (1.091 +/- 0.004 and 1.095 +/- 0.012 respectivly, P<0.01). However they had no effects on simulated ischemia and reperfusion-induced calcium overloading in normoxic myocytes. 50 microM pinacidil, a KATP opener, attenuated calcium overloading during ischemia and reperfusion in normoxic myocytes, but had no effect on [Ca2+]i change in IH myocytes. These results suggested that KATP channels contributed to the cardiac protection induced by IH against ischemia/reperfusion injury; the elimination of calcium overloading during ischemia/reperfusion by IH might underlie the mechanism of protection.
authors.affiliation: Laboratory of Hypoxic Cardiovascular Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320# YueYang Road, Shanghai 200031, PR China.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Zhu
authors.forename: Jian-Wen
authors.initials: JW
authors.lastname: Dong
authors.forename: Wei-Zhong
authors.initials: WZ
authors.lastname: Zhu
authors.forename: Hai-Lei
authors.initials: HL
authors.lastname: Ding
authors.forename: Zhao-Nian
authors.initials: ZN
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D003652:Decanoic Acids / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006880:Hydroxy Acids / Q000494:pharmacology; D000860:Hypoxia; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010477:Perfusion; D020110:Pinacidil / Q000494:pharmacology; D015221:Potassium Channels; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: D003652:Decanoic Acids; D006880:Hydroxy Acids; D008565:Membrane Proteins; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; C052853:5-hydroxydecanoic acid; D020110:Pinacidil; D005905:Glyburide; D002118:Calcium