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Mitochondrial ATP-sensitive K⁺ channels play a role in cardioprotection by Na⁺-H⁺ exchange inhibition against ischemia/reperfusion injury

Tetsuji Miura, MD, PhD^*, Yongge Liu, PhD, Mahiko Goto, MD, PhD^*, Akihito Tsuchida, MD, PhD^*, Takayuki Miki, MD, PhD^*, Atsushi Nakano, MD^*, Yasuhiro Nishino, MD^*, Yoshito Ohnuma, MD^* and Kazuaki Shimamoto, MD, PhD^*

^* Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
Maryland Research Laboratory, Otsuka America Pharmaceutical, Inc., Rockville, Maryland, USA

View larger version (30K): [in a new window]   Figure 1 Effects of cariporide on the time-course of the regional thickening fraction during repetitive ischemia and reperfusion. The thickening fraction after reperfusion was higher in the cariporide group than it was in the control group (Panel A) (p = 0.010 for group comparison and p < 0.001 for interaction). *p < 0.05 versus data at the corresponding time points. There was no significant difference in the time-courses of thickening fraction between the glib and glib/cariporide groups (Panel B) or between the 5-HD and 5-HD/cariporide groups (Panel C). Glib = glibenclamide; O1, O2, O3, O4 and O5 = first, second, third, fourth and fifth coronary occlusions, respectively; TF (% baseline) = the thickening fraction expressed as a percentage of baseline values; 5-HD = 5-hydroxydecanoate; Tx = treatment.

View larger version (17K): [in a new window]   Figure 2 Effects of diazoxide and EIPA on mitochondrial flavoprotein fluorescence and IK.ATP. Upper panel: although diazoxide (100 µM) induced oxidation of mitochondrial flavoprotein, EIPA (1 µM) did not provoke significant mitochondrial oxidation. Ethylisopropyl amiloride did not enhance mitochondrial oxidation by diazoxide. The flavoprotein fluorescence was calibrated by exposing the cells to 2,4-dinitrophenol (100 µM). Lower panel: data for IK.ATP measured at 0 mV. Neither diazoxide nor EIPA increased IK.ATP. EIPA = ethylisopropyl amiloride; IK.ATP = sarc-KATP channel current.