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大鼠视交叉上核神经元中一种快速激活型外向整流钾电流和A电流。

A rapidly activating type of outward rectifier K+ current and A-current in rat suprachiasmatic nucleus neurones.

作者信息

Bouskila Y, Dudek F E

机构信息

Department of Anatomy and Neurobiology, Colorado State University, Fort Collins 80523, USA.

出版信息

J Physiol. 1995 Oct 15;488 ( Pt 2)(Pt 2):339-50. doi: 10.1113/jphysiol.1995.sp020970.

Abstract
  1. The properties of calcium-independent (i.e. persisting in the absence of external calcium) depolarization-activated potassium currents in suprachiasmatic nucleus (SCN) neurones (n = 75) were studied under voltage-clamp conditions with whole-cell patch-clamp recordings in rat hypothalamic slices (150-175 microns). 2. Two distinct types of potassium currents were found. One was a rapidly activating and slowly inactivating type of outward rectifier (named IK(FR) for fast rectifier potassium current), similar to a potassium current described in cardiac muscle, and the other was a transient A-current (IA). 3. The rates of activation and deactivation of IK(FR) were voltage dependent. Time constants of activation fitted to n4 kinetics and declined from 3.5 ms (at -20 mV) to 1.1 ms (at 60 mV). Inactivation had a biexponential time course with voltage-independent time constants of 0.3 s (minor component) and 3.0 s (major component) between 10 and 50 mV. IK(FR) was activated above -40 mV with a V1/2 (membrane potential at half-maximal activation) of 14 +/- 2 mV and slope factor of -17 +/- 1 mV reaching a conductance (not maximal) of 10.8 +/- 1.7 nS at 60 mV. Steady-state inactivation had a slope factor of 11 +/- 1 mV. 4. IK(FR) was highly selective for K+ (PNa/PK = 0.002). Tetraethylammonium (TEA) reduced IK(FR) reversibly (IC50 = 20 mM), while 4-aminopyridine (4-AP) at 10 mM had little effect. The remaining current in 30 mM TEA was similar to that in control conditions, indicating that TEA reduced IK(FR) rather than revealed an additional TEA-resistant current. 5. The rate of IA activation was voltage dependent with time to peak declining from 8.5 ms (at -40 mV) to 3.6 ms (at 60 mV). Inactivation had a biexponential time course with voltage-dependent and voltage-independent time constants. The two components were similar in amplitude. IA was activated above -60 mV, reaching a maximal conductance of 3.6 +/- 0.4 nS at above 20 mV. Steady-state inactivation was complete above -10 mV. Rates of onset of inactivation (at -40 mV) and recovery from inactivation (at -100 mV) were similar with time constants of 39 +/- 5 and 41 +/- 9 ms, respectively. 6. IK(FR) and IA were found in every neurone tested in the SCN and in all locations throughout the nucleus. The possible function of these currents is discussed, particularly in relation to the circadian rhythm of firing rate in the SCN.
摘要
  1. 在电压钳制条件下,采用全细胞膜片钳记录技术,对大鼠下丘脑切片(150 - 175微米)中视交叉上核(SCN)神经元(n = 75)的非钙依赖性(即在无细胞外钙的情况下持续存在)去极化激活钾电流的特性进行了研究。2. 发现了两种不同类型的钾电流。一种是快速激活且缓慢失活的外向整流器类型(称为IK(FR),即快速整流钾电流),类似于心肌中描述的一种钾电流,另一种是瞬时A电流(IA)。3. IK(FR)的激活和失活速率均依赖于电压。激活时间常数符合n4动力学,从3.5毫秒(在 - 20毫伏时)降至1.1毫秒(在60毫伏时)。失活具有双指数时间进程,在10至50毫伏之间,电压无关的时间常数分别为0.3秒(次要成分)和3.秒(主要成分)。IK(FR)在 - 40毫伏以上被激活,V1/2(半最大激活时的膜电位)为14 ± 2毫伏,斜率因子为 - 17 ± 1毫伏,在60毫伏时达到电导(非最大值)10.8 ± 1.7纳安。稳态失活的斜率因子为11 ± 1毫伏。4. IK(FR)对K+具有高度选择性(PNa/PK = 0.002)。四乙铵(TEA)可逆性地降低IK(FR)(IC50 = 20毫摩尔),而10毫摩尔的4 - 氨基吡啶(4 - AP)几乎没有影响。在30毫摩尔TEA中的剩余电流与对照条件下的电流相似,表明TEA降低了IK(FR),而不是揭示了一种额外的TEA抗性电流。5. IA的激活速率依赖于电压,达到峰值的时间从8.5毫秒(在 - 40毫伏时)降至3.6毫秒(在60毫伏时)。失活具有双指数时间进程,其时间常数与电压有关和无关。两个成分的幅度相似。IA在 - 60毫伏以上被激活,在20毫伏以上达到最大电导3.6 ± 0.4纳安。稳态失活在 - 10毫伏以上完全完成。失活起始速率(在 - 40毫伏时)和从失活恢复速率(在 - 100毫伏时)相似,时间常数分别为39 ± 5毫秒和41 ± 9毫秒。IK(FR)和IA在SCN中测试的每个神经元以及整个核的所有位置均被发现。讨论了这些电流的可能功能,特别是与SCN中放电频率的昼夜节律的关系。

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