Role of mitochondrial permeability transition pore and mitochondrial ATP-sensitive potassium channels in the protective
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ORIGINAL PAPER
Role of mitochondrial permeability transition pore and mitochondrial ATP-sensitive potassium channels in the protective effects of ischemic preconditioning in isolated hearts from fed and fasted rats M. G. Marina Prendes & R. Hermann & M. E. Torresin & D. Vélez & E. A. Savino & A. Varela Received: 4 December 2013 / Accepted: 8 July 2014 / Published online: 19 July 2014 # University of Navarra 2014
Abstract The aim of the present study was to assess whether the protective effects of ischemic preconditioning (PC) are associated with activation of the mitochondrial ATP-sensitive potassium channels (mitoKATP) and if there is any relationship between the activity of these channels and the mitochondrial permeability transition pore (MPTP) opening in ischemic-reperfused rat hearts under different nutritional conditions. Langendorffperfused hearts of fed and 24-h fasted rats were exposed to 25 min of no-flow global ischemia plus 30 min of reperfusion. Fasting accelerated functional recovery and attenuated MPTP opening. The mitoKATP blocker, 5hydroxydecanoic (HD), did not influence functional recovery and MPTP opening induced by ischemia–reperfusion in the fed hearts but partially reversed the beneficial effects of fasting. PC and the mitoKATP opener, diazoxide (DZ), improved functional recovery, preserved cell viability, and inhibited MPTP opening in both fed and fasted hearts. The protection elicited by PC and DZ on contractile recovery and MPTP opening was reversed M. G. Marina Prendes (*) : R. Hermann : M. E. Torresin : D. Vélez : E. A. Savino : A. Varela Physiology Unit, Department of Biological Sciences, Faculty of Pharmacy and Biochemistry, University of Buenos Aires and IQUIMEFA-CONICET, 1113 Buenos Aires, Argentina e-mail: [email protected]
by HD, which did not affect cell viability. Altogether, these results argue for a role of mitoKATP and its impact on preservation mitochondrial inner membrane permeability as a relevant factor in the improvement of contractile function in the ischemic-reperfused rat heart. They also suggest that the functional protection elicited by PC may be related to this mechanism. Keywords Rat . Heart . Ischemia . Preconditioning . Mitochondrial-permeability-transition-pore . 5-Hydroxydecanoic . Fasting Abbreviations ANT Adenine nucleotide transporter C Control DMSO Dimethyl sulfoxide DZ Diazoxide HD 5-Hydroxydecanoic [3H]-22-Deoxy-[3H]-glucose DG mitoKATP Mitochondrial ATP-sensitive potassium channels MPTP Mitochondrial permeability transition pore PC Ischemic preconditioning
Introduction Present Address: M. G. Marina Prendes Cátedra de Fisiología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 Buenos Aires, Argentina
Brief intermittent ischemic periods separated by reperfusion prior to prolonged ischemia result in improved postischemic function and a highly significant reduction
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in infarct size. Although the protective effects of this phenomenon, called ischemic preconditioning (PC), have been amply described, the mechanisms involved a
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