MCC-134, a Blocker of Mitochondrial and Opener of Sarcolemmal ATP-Sensitive K+ Channels, Abrogates Cardioprotective Effects of Chronic Hypoxia

Title:

MCC-134, a Blocker of Mitochondrial and Opener of Sarcolemmal ATP-Sensitive K+ Channels, Abrogates Cardioprotective Effects of Chronic Hypoxia

Creator:

Kolář, F., Neckář, J., and Ošťádal, B.

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:51b5de09-2e88-4855-b2be-461833a47d92
uuid:51b5de09-2e88-4855-b2be-461833a47d92

Subject:

Chronic hypoxia, Ischemia/reperfusion, Cardioprotection, MCC-134, and KATP channels

Type:

article, model:article, and TEXT

Description:

We examined the effect of MCC-134, a novel inhibitor of mitochondrial ATP-sensitive K+ (mitoKATP) channels and activator of sarcolemmal ATP-sensitive K+ (sarcKATP) channels, on cardioprotection conferred by adaptation to chronic hypoxia. Adult male Wistar rats were exposed to intermittent hypobaric hypoxia (7000 m, 8 h/day, 5-6 weeks) and susceptibility of their hearts to ventricular arrhythmias and myocardial infarction was evaluated in anesthetized open-chest animals subjected to 20-min coronary artery occlusion and 3-h reperfusion on the day after the last hypoxic exposure. MCC-134 was administered intravenously 10 min before ischemia and 5 min before reperfusion in a total dose of 0.3 mg/kg or 3 mg/kg divided into two equal boluses. The infarct size (tetrazolium staining) was reduced from 59.2±4.4 % of the area at risk in normoxic controls to 43.2±3.3 % in the chronically hypoxic group. Chronic hypoxia decreased the reperfusion arrhythmia score from 2.4±0.5 in normoxic animals to 0.7±0.5. Both doses of MCC-134 completely abolished the antiarrhythmic protection (score 2.4±0.7 and 2.5±0.5, respectively) but only the high dose blocked the infarct size-limiting effect of chronic hypoxia (54.2±3.7 %). MCC-134 had no effect in the normoxic group. These results support the view that the opening of mitoKATP channels but not sarcKATP channels plays a crucial role in the mechanism by which chronic hypoxia improves cardiac tolerance to ischemia/reperfusion injury.

Language:

English

Rights:

http://creativecommons.org/licenses/by-nc-sa/4.0/
policy:public

Source:

Physiological research | 2005 Volume:54 | Number:4

Harvested from:

CDK

Metadata only:

false