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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Adenosine Triphosphate, Androgen Receptor Antagonists, Androstenedione, Animals, Biological Transport, Active, Cells, Cultured, Diazoxide, Flutamide, G Protein-Coupled Inwardly-Rectifying Potassium Channels, Ion Transport, Male, Membrane Proteins, Mitochondria, Heart, Mitochondrial Membrane Transport Proteins, Myocardial Ischemia, Myocytes, Cardiac, Patch-Clamp Techniques, Pinacidil, Potassium, Potassium Channels, Potassium Channels, Inwardly Rectifying, Rats, Rats, Sprague-Dawley, Sarcoplasmic Reticulum, Testosterone.
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Does testosterone induce cytoprotection by activating ATP-sensitive K+ channels in the cardiac mitochondrial inner membrane? Context: Whereas in the past, androgens were mainly believed to exert adverse effects on the cardiovascular system, recent experimental data postulate a benefit of testosterone for recovery of myocardial function after ischemia/reperfusion injury. Thus, we examined whether testosterone might improve myocardial tolerance to ischemia due to activation of mitochondrial (mitoK(ATP)) and/or sarcoplasmatic (sarcK(ATP)) K(ATP) channels. In a cellular model of ischemia, testosterone significantly decreased the rate of ischemia-induced death of cardiomyocytes that could be prevented by 5-hydroxydecainoic acid but was unaffected by the sarcK(ATP) blocker HMR1098 and the testosterone receptor antagonist flutamide. To index mitoK(ATP), mitochondrial flavoprotein fluorescence was measured. Testosterone induced a highly significant increase in mitochondrial flavoprotein fluorescence in intact myocytes and isolated mitoplasts that could be abolished by 5-hydroxydecainoic acid. Testosterone-mediated flavoprotein oxidation of mitoplasts was K+ dependent and ATP sensitive. In mitoplast-attached single-channel recordings, testosterone directly activated an ATP-sensitive K+ channel of the inner mitochondrial membrane. Addition of the K(ATP) channel opener diazoxide and pinacidil to the cytosolic solution activated the ATP-sensitive K+ current comparable to testosterone, whereas 5-hydroxydecainoic acid and glibenclamide inhibited the testosterone-induced current. Patch-clamp experiments of intact myocytes in whole-cell configuration did not demonstrate any effect of testosterone on sarcK(ATP) channels.
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Our results provide direct evidence for the existence of cardiac mitoK(ATP) and a link between testosterone-induced cytoprotection and activation of mitoK(ATP). Endogenous testosterone might play a more important role in recovery after myocardial infarction than is currently assumed. Final Decision: yes