AIMS: To investigate the role of the mitochondrial Ca(2+)-activated K(+) channel in cardioprotection induced by limb remote ischemic preconditioning. MAIN METHODS: Male Sprague-Dawley rats (250-300 g) were randomized into control, ischemia/reperfusion (I/R), remote ischemic preconditioning (RPC), NS1619 (a specific mitochondrial Ca(2+)-activated K(+) channel opener), and RPC+paxilline (a specific mitochondrial Ca(2+)-activated K(+) channel inhibitor) groups. RPC was induced by 4 cycles of 5 min of ligation followed by 5 min of reperfusion of the left femoral artery. Myocardial I/R was achieved by ligation of the left anterior descending coronary artery for 30 min, followed by 120 min of reperfusion. Infarct size was determined by 2,3,5-triphenyltetrazolium chloride staining, the hemodynamics were monitored, and lactate dehydrogenase (LDH) levels in the coronary effluent, manganese superoxide dismutase (Mn-SOD) content in mitochondria and mitochondrial membrane potential were measured spectrophotometrically. The ultrastructure of cardiomyocyte mitochondria was assessed by electron microscopy. KEY FINDINGS: NS1619 (10 μM) improved heart function, decreased infarct size, reduced LDH release, maintained mitochondrial structural integrity and mitochondrial membrane potential, and increased the mitochondrial content of Mn-SOD to the same degree as RPC treatment. However, paxilline (1 μM) eliminated the cardioprotective effect conferred by RPC. SIGNIFICANCE: The mitochondrial Ca(2+)-activated K(+) channel participates in the myocardial protection by limb remote ischemic preconditioning.
AIMS: To investigate the role of the mitochondrial Ca(2+)-activated K(+) channel in cardioprotection induced by limb remote ischemic preconditioning. MAIN METHODS: Male Sprague-Dawley rats (250-300 g) were randomized into control, ischemia/reperfusion (I/R), remote ischemic preconditioning (RPC), NS1619 (a specific mitochondrial Ca(2+)-activated K(+) channel opener), and RPC+paxilline (a specific mitochondrial Ca(2+)-activated K(+) channel inhibitor) groups. RPC was induced by 4 cycles of 5 min of ligation followed by 5 min of reperfusion of the left femoral artery. Myocardial I/R was achieved by ligation of the left anterior descending coronary artery for 30 min, followed by 120 min of reperfusion. Infarct size was determined by 2,3,5-triphenyltetrazolium chloride staining, the hemodynamics were monitored, and lactate dehydrogenase (LDH) levels in the coronary effluent, manganese superoxide dismutase (Mn-SOD) content in mitochondria and mitochondrial membrane potential were measured spectrophotometrically. The ultrastructure of cardiomyocyte mitochondria was assessed by electron microscopy. KEY FINDINGS: NS1619 (10 μM) improved heart function, decreased infarct size, reduced LDH release, maintained mitochondrial structural integrity and mitochondrial membrane potential, and increased the mitochondrial content of Mn-SOD to the same degree as RPC treatment. However, paxilline (1 μM) eliminated the cardioprotective effect conferred by RPC. SIGNIFICANCE: The mitochondrial Ca(2+)-activated K(+) channel participates in the myocardial protection by limb remote ischemic preconditioning.
Authors: Francesca Fiorentino; Gianni D Angelini; M-Saadeh Suleiman; Alima Rahman; Jon Anderson; Alan J Bryan; Lucy A Culliford; Marco Moscarelli; Prakash P Punjabi; Barnaby C Reeves Journal: Trials Date: 2015-04-23 Impact factor: 2.279
Authors: Xing-Huang Gao; Suparna Qanungo; Harish V Pai; David W Starke; Kelly M Steller; Hisashi Fujioka; Edward J Lesnefsky; Janos Kerner; Mariana G Rosca; Charles L Hoppel; John J Mieyal Journal: Redox Biol Date: 2013-11-12 Impact factor: 11.799
Authors: Derek J Hausenloy; Rainer Schulz; Henrique Girao; Brenda R Kwak; Diego De Stefani; Rosario Rizzuto; Paolo Bernardi; Fabio Di Lisa Journal: J Cell Mol Med Date: 2020-06-03 Impact factor: 5.310