Wladyka Cynthia L, Kunze Diana L
Rammelkamp Centre for Research and Education R326 MetroHealth Medical Centre, 2500 MetroHealth Drive, Cleveland, OH 44109-1998, USA.
J Physiol. 2006 Aug 15;575(Pt 1):175-89. doi: 10.1113/jphysiol.2006.113308. Epub 2006 Jun 15.
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 microM) and its analogue, XE991 (10 microM), 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 V1/2 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 microM), 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.
M电流是一种缓慢激活、非失活的钾电流，已证实在多种细胞类型中存在。在本研究中，通过免疫细胞化学研究，在大鼠结状神经节的内脏感觉神经元中鉴定出神经元M电流的分子相关物KCNQ2、Q3和Q5。所有神经元均显示这三种蛋白各自的表达。在电压钳研究中，认知增强药物利诺吡啶（1 - 50微摩尔）及其类似物XE991（10微摩尔）快速且不可逆地阻断了一种小的、缓慢激活的电流，该电流具有与KCNQ/M电流相似的动力学特性。这种电流在 - 60至 - 55毫伏之间激活，在 - 20毫伏时具有208±12毫秒的电压依赖性激活时间常数，在 - 50毫伏时具有165±24毫秒的失活时间常数，半激活电压（V1/2）为 - 24±2毫伏，这些值与先前关于内源性M电流的报道一致。在电流钳研究中，这些药物还导致静息膜电位在低至 - 60毫伏时发生去极化。氟吡汀（10 - 20微摩尔），一种M电流激活剂，使电流 - 电压关系向左移位3 - 14毫伏，并且还导致静息膜电位超极化。这些数据表明M电流存在于结状神经元中，在静息膜电位时被激活，并且在通过将细胞维持在负电压来调节兴奋性方面具有重要的生理意义。
