cGMP activates a pH-Sensitive leak K+ current in the presumed cholinergic neuron of basal forebrain
cGMP activates a pH-Sensitive leak K+ current in the presumed cholinergic neuron of basal forebrain
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DOI：
10.1152/jn.01051.2007
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发表时间：
2008-05-01
影响因子：
2.5
通讯作者：
Kang, Youngnam
中科院分区：
文献类型：
--
作者：
Toyoda, Hiroki;Saito, Mitsuru;Kang, Youngnam
在早期的研究中，我们证明，一氧化氮（NO）引起持久的膜超极化假定基底前脑胆碱能（BFC）神经元的cGMP-PKG依赖激活的泄漏钾电流在切片制备。在本研究中，我们研究了持久的膜超极化的离子机制，特别感兴趣的pH敏感性，因为8-Br-cGMP诱导的K+电流显示的Goldman-Hodgkin-Katz整流特性的TWIK-related acid-sensitive K+（ASK）通道。当用从-130 mV到-40 mV的斜坡命令脉冲去极化进行检查时，假定的BFC神经元显示出pH敏感性漏K+电流，其响应于pH从8.3降低到7.3比响应于pH从7.3降低到6.3更大。该K+电流在pH敏感性方面与TASK 1电流相似，而与TASK 1电流不同，它对Ba 2+高度敏感。8-Br-cGMP诱导的K+电流在假定的BFC神经元几乎完全抑制降低外部pH值为6.3，以及浴应用100 μ M的Ba 2+，与泄漏的K+电流的性质表示在假定的BFC神经元一致。在8-Br-cGMP应用后，通过pH从7.3降低到6.3获得的K+电流大于通过pH从8.3降低到7.3获得的K+电流，与对照条件中观察到的情况相反。这些观察结果强烈表明，8-Br-cGMP激活的pH-和Ba 2 + -敏感的泄漏K+电流表达在假定的BFC神经元通过调节其pH敏感性。
In an earlier study, we demonstrated that nitric oxide (NO) causes the long-lasting membrane hyperpolarization in the presumed basal forebrain cholinergic (BFC) neurons by cGMP-PKG-dependent activation of leak K+ currents in slice preparations. In the present study, we investigated the ionic mechanisms underlying the long-lasting membrane hyperpolarization with special interest in the pH sensitivity because 8-Br-cGMP-induced K+ current displayed Goldman-Hodgkin-Katz rectification characteristic of TWIK-related acid-sensitive K+ (TASK) channels. When examined with the ramp command pulse depolarizing from -130 to -40 mV, the presumed BFC neurons displayed a pH-sensitive leak K+ current that was larger in response to pH decrease from 8.3 to 7.3 than in response to pH decrease from 7.3 to 6.3. This K+ current was similar to TASK1 current in its pH sensitivity, whereas it was highly sensitive to Ba2+, unlike TASK1 current. The 8-Br-cGMP-induced K+ currents in the presumed BFC neurons were almost completely inhibited by lowering external pH to 6.3 as well as by bath application of 100 mu M Ba2+ , consistent with the nature of the leak K+ current expressed in the presumed BFC neurons. After 8-Br-cGMP application, the K+ current obtained by pH decrease from 7.3 to 6.3 was larger than that obtained by pH decrease from pH 8.3 to 7.3, contrary to the case seen in the control condition. These observations strongly suggest that 8-Br-cGMP activates a pH- and Ba2+ -sensitive leak K+ current expressed in the presumed BFC neurons by modulating its pH sensitivity.