Involvement of the phosphatidylinositol kinase pathway in augmentation of ATP-sensitive K+ channel currents by hypo-osmotic stress in rat ventricular myocytes

Hirofumi Mitsuyama, Hisashi Yokoshiki, Yuki Irie, Masaya Watanabe, Kazuya Mizukami, Hiroyuki Tsutsui

研究成果: ジャーナルへの寄稿記事

1 引用 (Scopus)

抄録

The objective of this study was to investigate the mechanisms of increase in the efficacy of ATP-sensitive K+ channel (KATP) openings by hypo-osmotic stress. The whole-cell KATP currents (Ik,atp) stimulated by 100 μmol/L pinacidil, a K+ channel opening drug, were significantly augmented during hypo-osmotic stress (189 mOsmol/L) compared with normal conditions (303 mOsmol/L). The EC50 and Emax value for pinacidil-activated Ik,atp (measured at 0 mV) was 154 μmol/L and 844 pA, respectively, in normal solution and 16.6 μmol/L and 1266 pA, respectively, in hypo-osmotic solution. Augmentation of IK ATP during hypo-osmotic stress was attenuated by wortmannin (50 μmol/L), an inhibitor of phosphatidylinositol 3- and 4-kinases, but not by (i) phalloidin (30 μmol/L), an actin filament stabilizer, (it) the absence of Ca2+ from the internal and external solutions, and (tit) the presence of creatine phosphate (3 mmol/L), which affects creatine kinase regulation of the KATP channels. In the single-channel recordings, an inside-out patch was made after approximately 5 min exposure of the myocyte to hypo-osmotic solution. However, the IC50 value for ATP under such conditions was not different from that obtained in normal osmotic solution. In conclusion, hypo-osmotic stress could augment cardiac Ik,atp through intracellular mechanisms involving the phosphatidylinositol kinase pathway.

元の言語英語
ページ(範囲)686-692
ページ数7
ジャーナルCanadian journal of physiology and pharmacology
91
発行部数9
DOI
出版物ステータス出版済み - 9 5 2013
外部発表Yes

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Osmotic Pressure
Phosphatidylinositols
Muscle Cells
Phosphotransferases
Adenosine Triphosphate
Pinacidil
KATP Channels
Phalloidine
Phosphocreatine
Creatine Kinase
Actin Cytoskeleton
Phosphatidylinositol 3-Kinases
Inhibitory Concentration 50
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pharmacology
  • Physiology (medical)

これを引用

Involvement of the phosphatidylinositol kinase pathway in augmentation of ATP-sensitive K+ channel currents by hypo-osmotic stress in rat ventricular myocytes. / Mitsuyama, Hirofumi; Yokoshiki, Hisashi; Irie, Yuki; Watanabe, Masaya; Mizukami, Kazuya; Tsutsui, Hiroyuki.

:: Canadian journal of physiology and pharmacology, 巻 91, 番号 9, 05.09.2013, p. 686-692.

研究成果: ジャーナルへの寄稿記事

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AU - Watanabe, Masaya

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AU - Tsutsui, Hiroyuki

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AB - The objective of this study was to investigate the mechanisms of increase in the efficacy of ATP-sensitive K+ channel (KATP) openings by hypo-osmotic stress. The whole-cell KATP currents (Ik,atp) stimulated by 100 μmol/L pinacidil, a K+ channel opening drug, were significantly augmented during hypo-osmotic stress (189 mOsmol/L) compared with normal conditions (303 mOsmol/L). The EC50 and Emax value for pinacidil-activated Ik,atp (measured at 0 mV) was 154 μmol/L and 844 pA, respectively, in normal solution and 16.6 μmol/L and 1266 pA, respectively, in hypo-osmotic solution. Augmentation of IK ATP during hypo-osmotic stress was attenuated by wortmannin (50 μmol/L), an inhibitor of phosphatidylinositol 3- and 4-kinases, but not by (i) phalloidin (30 μmol/L), an actin filament stabilizer, (it) the absence of Ca2+ from the internal and external solutions, and (tit) the presence of creatine phosphate (3 mmol/L), which affects creatine kinase regulation of the KATP channels. In the single-channel recordings, an inside-out patch was made after approximately 5 min exposure of the myocyte to hypo-osmotic solution. However, the IC50 value for ATP under such conditions was not different from that obtained in normal osmotic solution. In conclusion, hypo-osmotic stress could augment cardiac Ik,atp through intracellular mechanisms involving the phosphatidylinositol kinase pathway.

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