Interaction of sarcolemmal and mitochondrial ATP-sensitive K channel on cardioprotection

点击翻译按钮获取中文摘要

Ischemic Preconditioning is a phenomenon in which brief intermittent periods of ischemia are paradoxically protective against subsequent ischemic injury. To characterize the interaction sarcolemmal and mitochondrial ATP-sensitive K channel (KATP) on cardioprotection, we studied pretreatment effects of 2,4-dinitrophenol, a protonophore that uncouples mitochondrial respiration from ATP synthesis, on both flavoprotein oxidation, an index of mitochondrial uncoupling and sarcolemmal KATP activation in isolated rat ventricular myocytes. Effects of 5-hydroxydecanoic acid, a mitochondrial KATP inhibitor, on the pretreatment effects were also studied. Major findings of this study were that pretreatment of mitochondrial uncoupler sensitizes flavoprotein oxidation and sarcolemmal KATP activation. In the presence of 5-hydroxydecanoic acid the sensitizing effects were completely abolished. Without metabolic inhibition, sensitized myocardium represents almost normal flavoprotein oxidation and sarcol … More emmal KATP activity. These results suggest that, if we assume a memory molecule, direct effects of the memory molecule potentiates mitochondrial uncoupling and sarcolemmal KATP are negligible, but the memory molecule potentates mitochondrial uncoupling and sarcolemmal KATP in the face of metabolic impairment. In addition, the production of the memory molecule is 5-hydroxydecanoic acid-sensitive.Next, we evaluated the effects of isoflurane on the K_<ATP> channel activities in cultured rat smooth muscle cells. Openings of K_<ATP> channels were identified on the basis of the characteristic single-channel conductance (28±4pS), activation by 100 μM pinacidil, and block by 3 μM glibenclamide in cell-attached configuration. Application of isoflurane to bath solution during cell-attached recording significantly activated K_<ATP> channels. In contrast to cell-attached patches, isoflurane did not induced activation on K_<ATP> channel currents in outside-out patchclamp configuration. Isoflurane induced activation of K_<ATP> channels was abolished by a combination of PKA inhibitor peptide. Our results indicated that isoflurane activated K_<ATP> channels in rat smooth muscle cells via PKA activation K_<ATP> channel currents Less