Involvement of the phosphatidylinositol kinase pathway in augmentation of ATP-sensitive K+ channel currents by hypo-osmotic stress in rat ventricular myocytes.
Involvement of the phosphatidylinositol kinase pathway in augmentation of ATP-sensitive K+ channel currents by hypo-osmotic stress in rat ventricular myocytes.
复制标题
磷脂酰肌醇激酶途径参与大鼠心室肌细胞低渗应激引起的 ATP 敏感 K 通道电流增强。
DOI：
10.1139/cjpp-2012-0408
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
and Hiroyuki Tsutsui
中科院分区：
文献类型：
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作者：
Hirofumi Mitsuyama;Hisashi Yokoshiki;Yuki Irie;Masaya Watanabe;Kazuya Mizukami;and Hiroyuki Tsutsui
本研究的目的是探讨低渗透胁迫下atp敏感的K+通道（KATP）打开的功效增加的机制。低渗透胁迫下（189 mOsmol/L）的全细胞katp电流（IK，ATP）比正常条件下（303 mOsmol/L）明显增强。pinacid - activatedik、ATP（0 mV）在正常溶液中的ec50和demax值分别为154 μmol/L和844 pA，在低渗透溶液中的ec50和demax值分别为16.6 μmol/L和1266 pA。wortmannin （50 μmol/L）是一种磷脂酰肌醇3-和4-激酶抑制剂，可减弱低渗透胁迫下fik和atp的增加，但(i) phalloidin （30 μmol/L）是一种肌动蛋白丝稳定剂，（ii）内部和外部溶液中Ca2+的缺乏，（iii）磷酸肌酸（3 mmol/L）的存在影响肌酸激酶对katp通道的调节。在单通道记录中，在将肌细胞暴露于低渗透溶液中约5分钟后，制作一个由内向外的贴片。然而，在这种条件下，ATP的ic50值与在正常渗透溶液中获得的ic50值没有什么不同。综上所述，低渗透应激可通过磷脂酰肌醇激酶途径的细胞内机制增强心肌ik、atp。
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 KATPcurrents (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 EC50andEmaxvalue for pinacidil-activatedIK,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 ofIK,ATPduring 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 KATPchannels. 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 IC50value for ATP under such conditions was not different from that obtained in normal osmotic solution. In conclusion, hypo-osmotic stress could augment cardiacIK,ATPthrough intracellular mechanisms involving the phosphatidylinositol kinase pathway.