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

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Abstract

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.

Original languageEnglish
Pages (from-to)686-692
Number of pages7
JournalCanadian journal of physiology and pharmacology
Volume91
Issue number9
DOIs
Publication statusPublished - Sep 5 2013
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Physiology
  • Pharmacology
  • Physiology (medical)

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