Iberiotoxin-sensitive and -insensitive BK currents in Purkinje neuron somata
Iberiotoxin-sensitive and -insensitive BK currents in Purkinje neuron somata
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DOI：
10.1152/jn.00127.2012
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发表时间：
2013-05-01
影响因子：
2.5
通讯作者：
Raman, Indira M.
中科院分区：
文献类型：
--
作者：
Benton, Mark D.;Lewis, Amanda H.;Raman, Indira M.
浦肯野细胞具有产生高频动作电位的专门的内在离子电导。其Ca或Ca激活的K（K-Ca）电流的中断与体外放电模式的改变和体内运动行为的受损相关。为了研究体细胞K-Ca电流的特性，我们记录了从出生后17-21天的小鼠小脑分离的浦肯野细胞体的电压钳位K-Ca电流。电流由内源性Ca内流诱发，具有近似生理性的Ca缓冲。浦肯野胞体表达电压激活的镉敏感性K-Ca电流，其中IBTX敏感（>100 nS）和IBTX不敏感（>75 nS）成分。IBTX敏感电流在几毫秒内激活和部分失活。快速，不完全的宏观失活也很明显，在50或100赫兹列车的1毫秒去极化。与此相反，IBTX不敏感电流激活更慢，并没有闪烁。这些电流是不敏感的小和中等电导K-Ca通道阻断剂apamin，scyllatoxin，UCL 1684，荷包牡丹碱methiodide，和TRAM-34，但在很大程度上被1 mM的四乙基铵。基础通道的单通道电导接近150 pS，表明电流由IBTX抗性（含β（4））大电导K-Ca（BK）通道携带。IBTX不敏感的电流，但增加了小电导钾钙通道激动剂EBIO，氯唑沙宗，CyPPA。在列车的短暂去极化，IBTX不敏感的电流流动在interstep间隔，和积累的interstep外向电流增强EBIO。在电流钳，EBIO减缓尖峰，特别是在去极化电流注入。浦肯野细胞体的BK电流的两个成分可能对锋电位复极和放电频率有不同的贡献。此外，BK电流的增强可能部分地基于EBIO和氯唑沙宗的作用，以减轻与遗传性共济失调相关的破坏浦肯野细胞放电。
Purkinje cells have specialized intrinsic ionic conductances that generate high-frequency action potentials. Disruptions of their Ca or Ca-activated K (K-Ca) currents correlate with altered firing patterns in vitro and impaired motor behavior in vivo. To examine the properties of somatic K-Ca currents, we recorded voltage-clamped K-Ca currents in Purkinje cell bodies isolated from postnatal day 17-21 mouse cerebellum. Currents were evoked by endogenous Ca influx with approximately physiological Ca buffering. Purkinje somata expressed voltage-activated, Cd-sensitive K-Ca currents with iberiotoxin (IBTX)-sensitive (>100 nS) and IBTX-insensitive (>75 nS) components. IBTX-sensitive currents activated and partially inactivated within milliseconds. Rapid, incomplete macroscopic inactivation was also evident during 50- or 100-Hz trains of 1-ms depolarizations. In contrast, IBTX-insensitive currents activated more slowly and did not inactivate. These currents were insensitive to the small-and intermediate-conductance K-Ca channel blockers apamin, scyllatoxin, UCL1684, bicuculline methiodide, and TRAM-34, but were largely blocked by 1 mM tetraethylammonium. The underlying channels had single-channel conductances of similar to 150 pS, suggesting that the currents are carried by IBTX-resistant (beta(4)-containing) large-conductance K-Ca (BK) channels. IBTX-insensitive currents were nevertheless increased by small-conductance K Ca channel agonists EBIO, chlorzoxazone, and CyPPA. During trains of brief depolarizations, IBTX-insensitive currents flowed during interstep intervals, and the accumulation of interstep outward current was enhanced by EBIO. In current clamp, EBIO slowed spiking, especially during depolarizing current injections. The two components of BK current in Purkinje somata likely contribute differently to spike repolarization and firing rate. Moreover, augmentation of BK current may partially underlie the action of EBIO and chlorzoxazone to alleviate disrupted Purkinje cell firing associated with genetic ataxias.