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Title
  • en Involvement of the phosphatidylinositol kinase pathway in augmentation of ATP-sensitive K+ channel currents by hypo-osmotic stress in rat ventricular myocytes
Creator
    • en Mitsuyama, Hirofumi
    • en Irie, Yuki
    • en Watanabe, Masaya
    • en Mizukami, Kazuya
Accessrights open access
Subject
  • Other en hypo-osmotic stress
  • Other en ATP-sensitive K+ channels
  • Other en wortmannin
  • Other en phosphatidylinositol kinases
  • Other en K+ channel opening drug
  • Other en cardiomyocytes
  • NDC 490
Description
  • Abstract en 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.
Publisher en Canadian science publishing, nrc research press
Date
    Issued2013-09
Language
  • eng
Resource Type journal article
Version Type AM
Identifier HDL http://hdl.handle.net/2115/53391
Relation
  • URI http://www.nrcresearchpress.com/journal/cjpp
  • isVersionOf DOI https://doi.org/10.1139/cjpp-2012-0408
  • PMID 23984989
Journal
    • PISSN 0008-4212
    • NCID AA00597780
      • en Canadian journal of physiology and pharmacology
      • Volume Number91 Issue Number9 Page Start686 Page End692
File
Oaidate 2023-07-26