Sarcolemmal and mitochondrial effects of a KATP opener, P-1075, in 'polarized' and 'depolarized' Langendorff-perfused rat hearts
| Autor: | Olga Jilkina, Hee Jeong Kong, Bozena Kuzio, Valery Kupriyanov, Clifford D.L. Folmes, Gary J. Grover |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
ATP-sensitive potassium channel Pyridines Vasodilator Agents Biophysics Oxygen consumption Oxidative phosphorylation Mitochondrion Guanidines Biochemistry Phosphocreatine P-1075 Membrane Potentials Rats Sprague-Dawley chemistry.chemical_compound Sarcolemma Animals Membrane potential Calcium channel opener KATP opener Rb+/K+ efflux Heart Cell Biology Rubidium Potassium channel Mitochondria Rats chemistry Liver Heart Arrest Induced Potassium Sarcolemmal polarization Cytochrome c oxidase |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Biomembranes. 1618(1):39-50 |
| ISSN: | 0005-2736 |
| DOI: | 10.1016/j.bbamem.2003.10.004 |
| Popis: | We investigated consequences of cardiac arrest on sarcolemmal and mitochondrial effects of ATP-sensitive potassium channel (KATP) opener, P-1075, in Langendorff-perfused rat hearts. Depolarised cardiac arrest (24.7 mM KCl) did not affect glibenclamide-sensitive twofold activation of rubidium efflux by P-1075 (5 microM) from rubidium-loaded hearts, but eliminated uncoupling produced by P-1075 in beating hearts: 40% depletion of phosphocreatine and ATP, 50% increase in oxygen consumption, and reduction of cytochrome c oxidase. Depolarized cardiac arrest by calcium channel blocker, verapamil (5 microM), also prevented uncoupling. Lack of P-1075 mitochondrial effects in depolarized hearts was not due to changes in phosphorylation potential, because 2,4-dintrophenol (10 microM) reversed the [PCr]/[Cr] increase and Pi decrease, characteristic of KCl-arrest, but did not restore uncoupling. In agreement with this conclusion, pyruvate (5 mM) increased [PCr]/[Cr] and decreased Pi, but did not prevent uncoupling in beating hearts. A decrease in mean [Ca2+] in KCl-arrested hearts could not account for lack of P-1075 mitochondrial effects, because calcium channel opener, S-(-)-Bay K8644 (50 nM), and beta-agonist, isoproterenol (0.5 microM), did not facilitate uncoupling. In contrast, in adenosine (1 mM)-arrested hearts (polarized arrest), P-1075 caused 40% phosphocreatine and ATP depletion. In isolated rat liver mitochondria, P-1075 (20 microM) decreased mitochondrial membrane potential (DeltaPsi) by approximately 14 mV (demonstrated by redistribution of DeltaPsi-sensitive dye, rhodamine 800) in a glibenclamide-sensitive manner. We concluded that cell membrane depolarization does not prevent activation of sarcolemmal KATP by P-1075, but it plays a role in mitochondrial uncoupling effects of P-1075. |
| Databáze: | OpenAIRE |
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