Martens J R, Wang D, Sumners C, Posner P, Gelband C H
Department of Physiology, University of Florida, College of Medicine, Gainesville 32610, USA.
Circ Res. 1996 Aug;79(2):302-9. doi: 10.1161/01.res.79.2.302.
We have previously shown that angiotensin II (Ang II), via AT2 receptors, increases whole-cell K+ current in cultured rat hypothalamus and brain stern neurons. We have now investigated the AT2 receptor-mediated effects of Ang II on the activity of single delayed rectifier K+ channels in cell-attached membrane patches. In control recordings (bath, 5.4 mmol/L K+; pipette, 140 mmol/L K+), two voltage-dependent channels were recorded with conductances of 34 +/- 4 and 56 +/- 6 pS, respectively (n = 6). When patches were excised, the channels reversed near a membrane potential expected for a K+ channel. In cell-attached patches (-40 mV), Ang II (100 nmol/L) increased open probability of the 56-pS K+ channel from 0.03 +/- 0.01 to 0.21 +/- 0.05 (n = 3). The selective AT2 receptor antagonist PD 123319 (1 mumol/L) but not the AT1 receptor antagonist losartan (1 mumol/L) blocked the actions of Ang II (n = 3). The selective AT2 receptor agonist CGP 42112 (100 nmol/L) produced similar effects to Ang II. Kinetic analysis of the Ang II effect showed that open-time histograms were best fit by two exponential functions. Ang II increased both open-time constants relative to control (control, tau 1 = 0.9 +/- 0.1 milliseconds, tau 2 = 2.3 +/- 0.3 milliseconds; Ang II, tau 1 = 3.1 +/- 0.4 milliseconds, tau 2 = 12.1 +/- 2.4 milliseconds), and PD 123319 blocked this effect (n = 3). The closed-time histogram was not affected by Ang II PD 123319, or losartan. These results suggest that activation of AT2 receptors modulates rat hypothalamus and brain stern neuronal whole-cell K+ current by increasing the open probability of a 56-pS K+ channel.
我们之前已经表明，血管紧张素II（Ang II）通过AT2受体，增加培养的大鼠下丘脑和脑干神经元中的全细胞钾电流。我们现在研究了Ang II对细胞贴附膜片上单通道延迟整流钾通道活性的AT2受体介导作用。在对照记录中（浴槽中5.4 mmol/L钾；移液管中140 mmol/L钾），记录到两种电压依赖性通道，其电导分别为34±4和56±6 pS（n = 6）。当膜片被切除时，通道在钾通道预期的膜电位附近反转。在细胞贴附膜片（-40 mV）中，Ang II（100 nmol/L）使56-pS钾通道的开放概率从0.03±0.01增加到0.21±0.05（n = 3）。选择性AT2受体拮抗剂PD 123319（1 μmol/L）而非AT1受体拮抗剂氯沙坦（1 μmol/L）阻断了Ang II的作用（n = 3）。选择性AT2受体激动剂CGP 42112（100 nmol/L）产生了与Ang II相似的效应。对Ang II效应的动力学分析表明，开放时间直方图最适合用两个指数函数拟合。与对照相比，Ang II增加了两个开放时间常数（对照：τ1 = 0.9±0.1毫秒，τ2 = 2.3±0.3毫秒；Ang II：τ1 = 3.1±0.4毫秒，τ2 = 12.1±2.4毫秒），且PD 123319阻断了这种效应（n = 3）。关闭时间直方图不受Ang II、PD 123319或氯沙坦的影响。这些结果表明，AT2受体的激活通过增加56-pS钾通道的开放概率来调节大鼠下丘脑和脑干神经元的全细胞钾电流。
