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- Title
Involvement of the phosphatidylinositol kinase pathway in augmentation of ATP-sensitive K<sup>+</sup> channel currents by hypo-osmotic stress in rat ventricular myocytes.
- Authors
Mitsuyama, Hirofumi; Yokoshiki, Hisashi; Irie, Yuki; Watanabe, Masaya; Mizukami, Kazuya; Tsutsui, Hiroyuki
- 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, ( 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 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.
- Subjects
PHOSPHATIDYLINOSITOL 3-kinases; AUGMENTATION mammaplasty; ADENOSINE triphosphate; PHYSIOLOGICAL effects of potassium channels; VENTRICULAR remodeling; LABORATORY rats; OSMOTIC pressure
- Publication
Canadian Journal of Physiology & Pharmacology, 2013, Vol 91, Issue 9, p686
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/cjpp-2012-0408