Sarcolemmal and mitochondrial K(atp)channels mediate cardioprotection in chronically hypoxic hearts.
X. Kong, J. S. Tweddell, G. J. Gross and J. E. Baker. Sarcolemmal and Mitochondrial K(ATP)Channels Mediate Cardioprotection in Chronically Hypoxic Hearts. Journal of Molecular and Cellular Cardiology (2001) 33, 1041-1045. Hypoxia from birth increases the resistance of the isolated neonatal heart to ischemia. We determined if increased resistance to ischemia was due to activation of sarcolemmal or mitochondrial K(ATP)channels. Rabbits (n=8/group) were raised from birth in a normoxic (F(I)O(2)=0.21) or hypoxic (F(I)O(2)=0.12) environment for 8-10 days and the heart perfused with Krebs-Henseleit bicarbonate buffer. A mitochondrial-selective K(ATP)channel blocker 5-hydroxydecanoate (5-HD) (300 micromol/l) or a sarcolemmal-selective K(ATP)channel blocker HMR 1098 (30 micromol/l) were added alone or in combination for 20 min prior to a global ischemic period of 30 min, followed by 35 min reperfusion. Recovery of ventricular developed pressure was higher in chronically hypoxic than normoxic hearts. 5-HD and HMR 1098 partially reduced the cardioprotective effect of chronic hypoxia, but had no effect in normoxic hearts. The combination of 5-HD and HMR 1098 abolished the cardioprotective effect of chronic hypoxia. We conclude that both sarcolemmal and mitochondrial K(ATP)channels contribute to cardioprotection in the chronically hypoxic heart.
Kong
X
X
Division of Pediatric Surgery, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
Tweddell
J S
JS
Gross
G J
GJ
Baker
J E
JE
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D003652:Decanoic Acids / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D006439:Hemodynamics; D006880:Hydroxy Acids / Q000494:pharmacology; D000860:Hypoxia; D007511:Ischemia; D008928:Mitochondria / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010477:Perfusion; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D011817:Rabbits; D012508:Sarcolemma / Q000378:metabolism*; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D001549:Benzamides; D003652:Decanoic Acids; D006880:Hydroxy Acids; D015221:Potassium Channels; C052853:5-hydroxydecanoic acid; C410297:HMR 1098; D011188:Potassium; D010100:Oxygen