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Am J Physiol Heart Circ Physiol 281: H738-H744, 2001;
0363-6135/01 $5.00
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Vol. 281, Issue 2, H738-H744, August 2001

Selective blockade of mitochondrial KATP channels does not impair myocardial oxygen consumption

Yingjie Chen, Jay H. Traverse, Jianyi Zhang, and Robert J. Bache

Departments of Medicine and Radiology, University of Minnesota, Minneapolis, Minnesota 55455

Opening of mitochondrial ATP-sensitive potassium (KATP) channels has been postulated to prevent inhibition of respiration resulting from matrix contraction during high rates of ATP synthesis. Glibenclamide, which blocks KATP channels on the sarcolemma of vascular smooth muscle cells and myocardial myocytes as well as on the inner mitochondrial membrane, results in a decrease of myocardial oxygen consumption (MVO2) both at rest and during exercise. This study examined whether this represents a primary effect of blockade of mitochondrial KATP channels or occurs secondary to coronary resistance vessel constriction with a decrease of coronary blood flow (CBF) and myocardial oxygen availability. MVO2 was measured at rest and during treadmill exercise in 10 dogs during control conditions, after selective mitochondrial KATP channel blockade with 5-hydroxydecanoate (5-HD), and after nonselective KATP channel blockade with glibenclamide. During control conditions, exercise resulted in progressive increases of CBF and MVO2. Glibenclamide (50 µg · kg-1 · min-1 ic) resulted in a 17 ± 6% decrease of resting CBF with a downward shift of CBF during exercise and a decrease of coronary venous PO2, indicating increased myocardial oxygen extraction. In contrast with the effects of glibenclamide, 5-HD (0.7 mg · kg-1 · min-1 ic) had no effect on CBF, MVO2, or myocardial oxygen extraction. These findings suggest that glibenclamide decreased MVO2 by causing resistance vessel constriction with a decrease of CBF and oxygen available to the myocardium rather than to a primary reduction of mitochondrial respiration.

glibenclamide; 5-hydroxydecanoate; exercise; coronary blood flow


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