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

抄録

The objective of this study was to investigate the mechanisms of increase in the efficacy of ATP-sensitive K+ channel (K-ATP) openings by hypo-osmotic stress. The whole-cell K-ATP currents (I-K,I-ATP) stimulated by 100 mu mol/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 E-max value for pinacidil-activated I-K,I-ATP (measured at 0 mV) was 154 mu mol/L and 844 pA, respectively, in normal solution and 16.6 mu mol/L and 1266 pA, respectively, in hypo-osmotic solution. Augmentation of I-K,I-ATP during hypo-osmotic stress was attenuated by wortmannin (50 mu mol/L), an inhibitor of phosphatidylinositol 3- and 4-kinases, but not by (i) phalloidin (30 mu mol/L), an actin filament stabilizer, (ii) the absence of Ca2+ from the internal and external solutions, and (iii) the presence of creatine phosphate (3 mmol/L), which affects creatine kinase regulation of the K-ATP 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 I-K,I-ATP through intracellular mechanisms involving the phosphatidylinositol kinase pathway.

収録刊行物

• Canadian journal of physiology and pharmacology

  Canadian journal of physiology and pharmacology 91 (9), 686-692, 2013-09

  Canadian science publishing, nrc research press

キーワード

• hypo-osmotic stress
• ATP-sensitive K+ channels
• wortmannin
• phosphatidylinositol kinases
• K+ channel opening drug
• cardiomyocytes

詳細情報

• CRID: 1050282813991179904
• NII論文ID: 120005333605
• NII書誌ID: AA00597780
• HANDLE: 2115/53391
• ISSN: 00084212
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles