The Effects of K^+ Channels Modulators Terikalant and Glibenclamide on Membrane Potential Changes Induced by Hypotonic Challenge of Guinea Pig Ventricular Myocytes
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概要
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Contribution of inward rectifier K+ currents (IK1) and ATP-sensitive K+ currents (IKATP) to membrane potential changes of ventricular myocytes appearing during hypotonic challenge is unclear. We used here the whole cell patch clamp technique, voltage and current clamp modes, to record membrane potentials and ionic currents in isolated guinea pig ventricular myocytes under isotonic or hypotonic perfusion. The difference in osmolarity between iso- and hypotonic solutions was about 100 mOsm. Exposure to hypotonic solution for 60 s induced initial prolongation of action potential duration at 90% of repolarization (APD90) (from 176 ± 10 to 189 ± 11 ms, P<0.05, n = 13). Further perfusion for the next 300 s shorthened APD90 to 135 ± 9 ms (P<0.01, in comparison with control values, n = 13) and depolarized resting potential from −79.2 ± 1.5 to −75.0 ± 0.9 mV, (P<0.05, n = 13). Neither pretreatment with a blocker of IK1 channels, terikalant at 10 μM, nor with a blocker of IKATP channels, glibenclamide at 1 μM, prevented the above-mentioned changes in membrane potential induced by hypotonic challenge when a pipette solution containing 5 mM ATP was used. Also, glibenclamide and terikalant did not affect the hypotonic-sensitive current, obtained by ramp or voltage-step protocols, respectively. Additionally, the current-voltage relationship (I-V curve) of the whole cell hypotonic-sensitive current shifted from an isotonic I-V curve in a parallel way. Our results indicate that IK1 and IKATP do not participate in membrane potential changes induced by hypotonic solution at least in the guinea pig ventricular myocytes with sufficient intracellular ATP.
- 社団法人 日本薬理学会の論文
- 2004-05-20
著者
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HIRAOKA Masayasu
Department of Cardiovascular Medicine, Tokyo Medical and Dental University
-
Higashiuesato Yasushi
東京医科歯科大学 分子病態学
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Matsuda Hisao
Kawasaki Municipal Tama Hospital Cardiovascular Division
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Hirano Yuji
Department of Cardiovascular Diseases MRI, Tokyo Medical and Dental University
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Hiraoka Masayasu
Department Of Cardiovascular Disease Medical Research Institute Tokyo Medical And Dental University
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KOCIC Ivan
Department of Cardiovascular Diseases, Medical Research Institute, Tokyo Medical and Dental Universi
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Kocic Ivan
Department Of Cardiovascular Disease Medical Research Institute Tokyo Medical And Dental University
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Hiraoka Masayasu
Department Of Cardilvascular Disease Medical Research Institute Tokyo Medical And Dental University
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Hirano Yuji
Department Of Cardiovascular Disease Medical Research Institute Tokyo Medical And Dental University
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Hirano Yuji
Department of Cardiovascular Disease, Medical Research Institute, Tokyo Medical and Dental University
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