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Gating currents from neuronal K(V)7.4 channels: general features and correlation with the ionic conductance.
Channels (Austin, Tex.) Pub Date : 2009-07-09
Francesco Miceli 1 , Maria Roberta Cilio , Maurizio Taglialatela , Francisco Bezanilla
Affiliation  

The K(V)7 (KCNQ) subfamily of voltage-gated K(+) channels consists of five members (K(V)7.1-K(V)7.5) giving rise to non-inactivating, and slowly activating/deactivating currents mainly expressed in cardiac (K(V)7.1) and neuronal (K(V)7.2-K(V)7.5) tissue. In the present study, using the cut-open oocyte voltage clamp, we studied the relation of the ionic currents from homomeric neuronal K(V)7 channels (K(V)7.2-K(V)7.5) with the gating currents recorded after K(+) conductance blockade from the same channels. Increasing the recording temperature from 18 degrees C to 28 degrees C accelerated activation/deactivation kinetics of the ionic currents in all homomeric K(V)7 channels (activation Q(10)s at 0 mV were 3.8, 4.1, 8.3 and 2.8 for K(V)7.2, K(V)7.3, K(V)7.4 and K(V)7.5 channels, respectively), without large changes in currents voltage-dependence; moreover, at 28 degrees C, ionic currents carried by K(V)7.4 channels also showed a significant increase in their maximal value. Gating currents were only resolved in K(V)7.4 and K(V)7.5 channels; the size of the ON gating charges at +40 mV was 1.34 +/- 0.34 nC for K(V)7.4, and 0.79 +/- 0.20 nC for K(V)7.5. At 28 degrees C, K(V)7.4 gating currents had the following salient properties: (1) similar time integral of Q(ON) and Q(OFF), indicating no charge immobilization; (2) a left-shift in the V(1/2) of the Q(ON)/V when compared to the G/V (approximately 50 mV in the presence of 2 mM extracellular Ba(2+)); (3) a Q(ON) decay faster than ionic current activation; and (4) a rising phase in the OFF gating charge after depolarizations larger than 0 mV. These observations suggest that, in K(V)7.4 channels, VSD movement is followed by a slow and/or low bearing charge step linking to pore opening, a result which may help to clarify the molecular consequence of disease-causing mutations and drugs affecting channel gating.

中文翻译:

来自神经元 K(V)7.4 通道的门控电流:一般特征和与离子电导的相关性。

电压门控 K(+) 通道的 K(V)7 (KCNQ) 亚家族由五个成员 (K(V)7.1-K(V)7.5) 组成,主要产生非失活和缓慢激活/失活电流在心脏 (K(V)7.1) 和神经元 (K(V)7.2-K(V)7.5) 组织中表达。在本研究中,使用切开的卵母细胞电压钳,我们研究了来自同聚神经元 K(V)7 通道 (K(V)7.2-K(V)7.5) 的离子电流与之后记录的门控电流的关系。来自相同通道的 K(+) 电导阻滞。将记录温度从 18 摄氏度提高到 28 摄氏度可加速所有同聚 K(V)7 通道中离子电流的激活/失活动力学(0 mV 时的激活 Q(10)s 为 3.8、4.1、8.3 和 2.8,K (V)7.2、K(V)7.3、K(V)7.4 和 K(V)7.5 通道),电流电压依赖性没有大的变化;此外,在 28 摄氏度时,K(V)7.4 通道携带的离子电流也显示出其最大值的显着增加。门控电流仅在 K(V)7.4 和 K(V)7.5 通道中解析;对于 K(V)7.4,+40 mV 处的 ON 门控电荷的大小为 1.34 +/- 0.34 nC,对于 K(V)7.5 为 0.79 +/- 0.20 nC。在 28 摄氏度时,K(V)7.4 门控电流具有以下显着特性:(1) Q(ON) 和 Q(OFF) 的时间积分相似,表明没有电荷固定;(2) 与 G/V 相比,Q(ON)/V 的 V(1/2) 左移(在 2 mM 细胞外 Ba(2+) 存在下约为 50 mV);(3) Q(ON) 衰减快于离子电流激活;(4) 去极化大于 0 mV 后,OFF 门控电荷的上升阶段。这些观察结果表明,在 K(V)7.4 通道中,
更新日期:2019-11-01
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