Mechanism of Na^+/Ca^<2+> Exchanger Activation by Hydrogen Peroxide in Guinea-Pig Ventricular Myocytes
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概要
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Using the whole-cell voltage clamp, we examined the mechanism of activation of the Na+/Ca2+ exchanger (NCX) by hydrogen peroxide (H2O2) in isolated guinea-pig cardiac ventricular myocytes. Exposure to H2O2 increased the NCX current. The effect was inhibited by cariporide, an inhibitor of the Na+/H+ exchanger (NHE), suggesting that there are NHE-dependent and -independent pathways in the effect of H2O2 on NCX. In addition, both pathways were blocked by edaravone, a hydroxyl radical (•OH) scavenger; pertussis toxin, a Gi/o protein inhibitor; and U0126, an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK). On the other hand, wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, inhibited only the NHE-dependent pathway, while PP2, a Src family protein tyrosine kinase inhibitor, inhibited only the NHE-independent pathway. Taken together, our data suggest that H2O2 increases the NCX current via two signal transduction pathways. The common pathway is the conversion of H2O2 to •OH, which activates Gi/o protein and a mitogen-activated protein (MAP) kinase signaling pathway. Then, one pathway activates NHE with a PI3K-dependent mechanism and indirectly increases the NCX current. Another pathway involves activation of a Src family tyrosine kinase.
- 社団法人 日本薬理学会の論文
- 2007-03-20
著者
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Kimura Junko
Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University
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Wakabayashi Yasushi
Department of Medicine III, Hamamatsu University School of Medicine
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Iwamoto Takahiro
Department of Pharmacology, Fukuoka University
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Kimura J
Dep. Of Pharmacology School Of Medicine Fukushima Medical Univ. Jpn
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Watanabe Yasuhide
Division of Nursing, Hamamatsu University School of Medicine
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Iwamoto Takahiro
Department Of Pharmacology Fukuoka University School Of Medicine
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Iwamoto Takahiro
Department Of Medical Engineering And Cardiology Institute Of Development Aging And Cancer Tohoku Un
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Watanabe Yasuhide
Department Of Pharmacology School Of Medicine Fukushima Medical University
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Kimura J
Department Of Pharmacology Fukushima Medical University School Of Medicine
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MATSUOKA Isao
Department of Pharmacology, Fukushima Medical University, School of Medicine
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Matsuoka Isao
Department Of Pharmacology Fukushima Medical College
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HINATA Masamitsu
Department of Pharmacology, Fukushima Medical University, School of Medicine
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Wakabayashi Yasushi
Department Of Pharmacology School Of Medicine Fukushima Medical University
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Hinata Masamitsu
Department Of Pharmacology Fukushima Medical University School Of Medicine
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Matsuoka Isao
Department Of Anesthesiology Ilikai Medical Inc Kakizoe Hospital
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