Opioid Receptors, KATP Channels and Ischemic Preconditioning
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ATP-gated potassium channels (KATP) were initially identified in the myocardium by Noma1 using patch clamp methodology in isolated guinea pig ventricular myocytes. Since its discovery, a number of factors and endogenous substances such as the ATP/ADP ratio, certain nucleotide diphosphates, Mg++, lactate, pH, protein kinase C, adenosine and bradykinin have been shown to modulate the gating properties of this channel in the heart.2 Since KATP channel activity is regulated by the metabolic state of the myocardial cell, Noma1 originally proposed that this channel would serve an endogenous cardioprotective function. Subsequently, it was shown that KATP channel opening produced by ischemia resulted in certain characteristic electrophysiological alterations including a shortening of the ventricular action potential duration (APD) and an attenuation of the rate of membrane depolarization. These changes would be expected to result in a decreased rate of calcium influx via voltage-sensitive calcium channels and sodium-calcium exchange and reduce calcium overload and lethal cell injury if timely reperfusion were to occur. A number of studies support this hypothesis, although several recent reports suggest that APD shortening is not essential in mediating the cardioprotective effect of KATP channel opening against myocardial infarction or stunning.3’4 Nevertheless, based upon numerous studies from several laboratories and several species, there is little doubt that the KATP channel serves an important cardioprotective role during ischemic or hypoxic insults.
KeywordsInfarct Size Opioid Receptor KATP Channel Ischemic Precondition Cardioprotective Effect
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