Activation of protein kinase A partially reverses the effects of 2,3-butanedione monoxime on the transient outward K+ current of rat ventricular myocytes.
Activation of protein kinase A partially reverses the effects of 2,3-butanedione monoxime on the transient outward K+ current of rat ventricular myocytes.
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蛋白激酶 A 的激活部分逆转了 2,3-丁二酮单肟对大鼠心室肌细胞瞬时外向 K 电流的影响。
DOI：
10.1016/0024-3205(95)00292-e
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发表时间：
1995
期刊：
影响因子：
6.1
通讯作者：
McArdle,JJ
中科院分区：
文献类型：
--
作者：
Xiao,YF;McArdle,JJ
用全细胞膜片钳技术记录单个大鼠心室肌细胞的瞬时外向钾电流(Ito)。胞外应用化学磷酸酶2，3-丁二酮单肟(BDM)以浓度依赖的方式抑制Itoin。IC50为14 mm。这一效应出现在涂药后20天内的S。BDM冲洗后2分钟基本恢复正常。20 mM BDM使Ito稳态失活曲线负移9±2 mV(n=8)。加入5μM异丙肾上腺素后，Ito幅度增加16.2±1.8%。此浓度的异丙肾上腺素部分逆转了BDM对Ito的抑制作用。此外，应用10 mM 8-溴腺苷3‘：5’-环一磷酸可增强Ito的幅度，并显著逆转BDM对Ito的抑制作用。而3‘：5’-环一磷酸鸟苷(cGMP，1-10 mM)细胞内透析不影响BDM对Ito的抑制作用。内向整流钾电流(Ik1)对BDM相对不敏感，即20 mM BDM对Ito1和Ik1的抑制分别为对照组的35.5±4.3%(n=8)和92.9±4.0%(n=4)。上述结果表明，BDM对大鼠心室肌细胞Ito1有抑制作用，但对Ik1无抑制作用。我们将BDM对Itoo的抑制归因于通道蛋白的去磷酸化。
The transient outward K+current (Ito) was assessed in single rat ventricular myocytes with the whole-cell patch-clamp technique. Extracellular application of the chemical phosphatase 2,3-butanedione monoxime (BDM) inhibited Itoin a concentration-dependent manner. The IC50, was 14 mM. The on-set of this effect occurred within 20 s after BDM application. Itorecovered almost completely at 2 min after washout of BDM. Application of 20 mM BDM shifted the steady-state inactivation curve of Itoby 9 ± 2 mV (n = 8) in the negative direction. Addition of 5 μM isoproterenol enhanced Itoamplitude by 16.2 ± 1.8%. This concentration of isoproterenol partially reversed the BDM-induced inhibition of Ito. Furthermore, application of 10 mM 8-bromo-adenosine 3′:5′-cyclic monophosphate enhanced the amplitude of Itoand also significantly reversed the BDM-induced suppression of Ito. In contrast, intracellular dialysis with guanosine 3′:5′-cyclic monophosphate (cGMP, 1–10 mM) did not affect the BDM-induced inhibition of Ito. The inward rectifier K+current (Ik1) was relatively insensitive to BDM; i.e., 20 mM BDM inhibited Itoand Ik1to 35.5 ± 4.3% (n = 8) and 92.9 ± 4.0% (n = 4) of the control, respectively. These results indicate that BDM suppressed Itobut not Ik1of rat ventricular myocytes. We attribute the BDM suppression of Itoto dephosphorylation of the channel protein.