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由蛋白激酶A和一种G蛋白调节的单个心脏外向整流钾通道

Single cardiac outwardly rectifying K+ channels modulated by protein kinase A and a G-protein.

作者信息

Benz I, Fröbe U, Kohlhardt M

机构信息

Physiologisches Institut, Universität Freiburg, Federal Republic of Germany.

出版信息

Eur Biophys J. 1991;20(5):281-6. doi: 10.1007/BF00450563.

DOI:10.1007/BF00450563
PMID:1782909
Abstract

Elementary K+ currents were recorded at 19 degrees C in cell-attached and in inside-out patches excised from neonatal rat heart myocytes. An outwardly rectifying K+ channel which prevented Na+ ions from permeating could be detected in about 10% of the patches attaining (at 5 mmol/l external K+ and between -20 mV and +20 mV) a unitary conductance of 66 +/- 3.9 pS. K+(outw.-rect.) channels have one open and at least two closed states. Open probability and tau open rose steeply on shifting the membrane potential in the positive direction, thereby tending to saturate. Open probability (at -7 mV) was as low as 3 +/- 1% but increased several-fold on exposing the cytoplasmic surface to Mg-ATP (100 mumol/l) without a concomitant change of tau open. No channel activation occurred in response to ATP in the absence of cytoplasmic Mg++. The cytoplasmic administration of the catalytic subunit of protein kinase A (120-150 mu/ml) or GTP-gamma-S (100 mumol/l) caused a similar channel activation. GDP-beta-S (100 mumol/l) was also tested and found to be ineffective in this respect. This suggests that cardiac K+(outw.-rect.) channels are metabolically modulated by both cAMP-dependent phosphorylation and a G-protein.

摘要

在19摄氏度下,对新生大鼠心脏心肌细胞进行细胞贴附式和内面向外膜片钳记录,检测到基本的钾离子电流。在约10%的膜片中(在外部钾离子浓度为5 mmol/L且膜电位在-20 mV至+20 mV之间),可检测到一种阻止钠离子通透的外向整流钾离子通道,其单通道电导为66±3.9 pS。钾离子(外向整流)通道有一个开放状态和至少两个关闭状态。当膜电位向正向移动时,开放概率和开放时间常数急剧上升,趋于饱和。在-7 mV时开放概率低至3±1%,但在将细胞质表面暴露于Mg-ATP(100 μmol/L)时增加了几倍,而开放时间常数没有相应变化。在没有细胞质Mg++的情况下,ATP不会引起通道激活。向细胞质中加入蛋白激酶A的催化亚基(120 - 150 μ/ml)或GTP-γ-S(100 μmol/L)会引起类似的通道激活。还测试了GDP-β-S(100 μmol/L),发现其在这方面无效。这表明心脏钾离子(外向整流)通道受到cAMP依赖性磷酸化和G蛋白的代谢性调节。

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引用本文的文献

1
Characterization of the sensitivity of cardiac outwardly-rectifying K+ channels to class III antiarrhythmics: the influence of inhibitory sulfonamide derivatives.心脏外向整流钾通道对Ⅲ类抗心律失常药物敏感性的特征:抑制性磺酰胺衍生物的影响。
Naunyn Schmiedebergs Arch Pharmacol. 1995 Sep;352(3):313-21. doi: 10.1007/BF00168563.
2
Thermodynamically specific gating kinetics of cardiac mammalian K+(ATP) channels in a physiological environment near 37 degrees C.在接近37摄氏度的生理环境中,心脏哺乳动物K+(ATP)通道的热力学特异性门控动力学。
J Membr Biol. 1995 Jul;146(1):85-90. doi: 10.1007/BF00232682.
3
Blockade of cardiac outwardly rectifying K+ channels by TEA and class III antiarrhythmics--evidence against a single drug-sensitive channel site.

本文引用的文献

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The ionic basis of concentration-related effects of noradrenaline on the action potential of calf cardiac purkinje fibres.去甲肾上腺素对小牛心脏浦肯野纤维动作电位浓度相关效应的离子基础。
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