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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Medicine / Faculty of Medicine >
Peer-reviewed Journal Articles, etc >
Involvement of the phosphatidylinositol kinase pathway in augmentation of ATP-sensitive K+ channel currents by hypo-osmotic stress in rat ventricular myocytes
| Title: | Involvement of the phosphatidylinositol kinase pathway in augmentation of ATP-sensitive K+ channel currents by hypo-osmotic stress in rat ventricular myocytes |
| Authors: | Mitsuyama, Hirofumi Browse this author | | Yokoshiki, Hisashi Browse this author →KAKEN DB | | Irie, Yuki Browse this author | | Watanabe, Masaya Browse this author | | Mizukami, Kazuya Browse this author | | Tsutsui, Hiroyuki Browse this author →KAKEN DB |
| Keywords: | hypo-osmotic stress | | ATP-sensitive K+ channels | | wortmannin | | phosphatidylinositol kinases | | K+ channel opening drug | | cardiomyocytes |
| Issue Date: | Sep-2013 |
| Publisher: | Canadian science publishing, nrc research press |
| Journal Title: | Canadian journal of physiology and pharmacology |
| Volume: | 91 |
| Issue: | 9 |
| Start Page: | 686 |
| End Page: | 692 |
| Publisher DOI: | 10.1139/cjpp-2012-0408 |
| PMID: | 23984989 |
| 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,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. |
| Relation: | http://www.nrcresearchpress.com/journal/cjpp |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/53391 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 横式 尚司
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