KCNQ/M-currents contribute to the resting membrane potential in rat visceral sensory neurons
KCNQ/M-currents contribute to the resting membrane potential in rat visceral sensory neurons
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DOI：
10.1113/jphysiol.2006.113308
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发表时间：
2006-08-15
影响因子：
5.5
通讯作者：
Kunze, Diana L.
中科院分区：
文献类型：
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作者：
Wladyka, Cynthia L.;Kunze, Diana L.
M-电流是一种缓慢激活、非失活的钾电流，已被证明存在于多种细胞类型中。本研究通过免疫细胞化学方法，在大鼠结状神经节内脏感觉神经元中鉴定了神经元M-电流的相关分子KCNQ2、Q3和Q5。所有神经元均表达上述三种蛋白。在电压钳研究中，认知增强剂利诺匹定(1-50微米)及其类似物XE991(10微米)可迅速、不可逆地阻断一种与KCNQ/M-电流具有相似动力学特性的缓慢激活的小电流。该电流在-60~-55 mV之间激活，在-20 mV时的电压依赖性激活时间常数为208+/-12ms，在-50 mV时的失活时间常数为165+/-24ms，V-1/2为-24+/-2 mV，与已报道的内源性M电流的值一致。在目前的钳制研究中，这些药物还导致静息膜电位的去极化，负值为-60 mV。M电流激动剂Flupirtin(10-20 mU M)使电流-电压关系左移3-14 mV，并引起静息膜电位超极化。这些数据表明，M-电流存在于结状神经元，在静止膜电位时被激活，并通过维持细胞在负电压下而在调节兴奋性方面具有重要的生理学意义。
The M-current is a slowly activating, non-inactivating potassium current that has been shown to be present in numerous cell types. In this study, KCNQ2, Q3 and Q5, the molecular correlates of M-current in neurons, were identified in the visceral sensory neurons of the nodose ganglia from rats through immunocytochemical studies. All neurons showed expression of each of the three proteins. In voltage clamp studies, the cognition-enhancing drug linopirdine (1-50 mu M) and its analogue, XE991 (10 mu M), quickly and irreversibly blocked a small, slowly activating current that had kinetic properties similar to KCNQ/M-currents. This current activated between -60 and -55 mV, had a voltage-dependent activation time constant of 208 +/- 12 ms at -20 mV, a deactivation time constant of 165 +/- 24 ms at -50 mV and V-1/2 of -24 +/- 2 mV, values which are consistent with previous reports for endogenous M-currents. In current clamp studies, these drugs also led to a depolarization of the resting membrane potential at values as negative as -60 mV. Flupirtine (10-20 mu M), an M-current activator, caused a 3-14 mV leftward shift in the current-voltage relationship and also led to a hyperpolarization of resting membrane potential. These data indicate that the M-current is present in nodose neurons, is activated at resting membrane potential and that it is physiologically important in regulating excitability by maintaining cells at negative voltages.