Topics on the Na^+/Ca^<2+> Exchanger : Pharmacological Characterization of Na^+/Ca^<2+> Exchanger Inhibitors
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概要
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Using the whole-cell voltage clamp, we examined acute effects of various agents on Na+/Ca2+ exchange current (INCX) in guinea-pig cardiac ventricular cells and transfected cells. Among the antiarrhythmic drugs, amiodarone, bepridil, dronedarone, cibenzoline, azimilide, and aprindine inhibited INCX in a concentration-dependent manner. We also investigated the effects on NCX of 2,3-buanedione monoxim (BDM) and selective NCX inhibitors such as KB-R7943, SEA0400, and SN-6. The presence of trypsin in the pipette solution attenuated the inhibitory effects on NCX of amiodarone, bepridil, and BDM, suggesting that these drugs inhibit NCX from the cytosolic side. In contrast, the trypsin-insensitive NCX inhibitors were aprindine, azimilide, dronedarone, cibenzoline, KB-R7943, SEA0400, and SN-6. KB-R7943, SEA0400, and SN-6 suppressed the uni-directional outward INCX more potently than the uni-directional inward INCX. The mechanism of this mode-dependency is unknown, but is suggested to be related to intracellular Na+ concentration.
- 社団法人 日本薬理学会の論文
- 2006-09-20
著者
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Kimura Junko
Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University
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Koide Yuuki
Lab. Of Organic Chemistry Graduate School Of Pharmaceutical Sciences Chiba Univ. Jpn
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Watanabe Yasuhide
Division of Nursing, Hamamatsu University School of Medicine
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Watanabe Yasuhide
Division Of Pathophysiology Basic Nursing Hamamatsu University School Of Medicine
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Kimura Junko
Dep. Of Pharmacology School Of Medicine Fukushima Medical Univ. Jpn
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KOIDE Yuuki
Drug Research Department, Tokyo Research Laboratories, TOA EIYO Ltd.
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