In:
Canadian Journal of Physiology and Pharmacology, Canadian Science Publishing, Vol. 91, No. 9 ( 2013-09), p. 686-692
Abstract:
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,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 EC 50 and E max value for pinacidil-activated I K,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 I K,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 Ca 2+ 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 IC 50 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,ATP through intracellular mechanisms involving the phosphatidylinositol kinase pathway.
Type of Medium:
Online Resource
ISSN:
0008-4212
,
1205-7541
DOI:
10.1139/cjpp-2012-0408
Language:
English
Publisher:
Canadian Science Publishing
Publication Date:
2013
detail.hit.zdb_id:
2004356-9
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