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

机译:大鼠视交叉上核神经元的快速激活型向外整流子K +电流和A-电流。

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摘要

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.
机译:1.在全电压膜片钳记录下,在电压钳制条件下研究了视交叉上核(SCN)神经元(n = 75)中非钙依赖性(即在没有外部钙的情况下持续存在)去极化激活的钾电流的性质。在大鼠下丘脑切片(150-175微米)中。 2.发现了两种不同类型的钾电流。一种是快速激活和缓慢失活的外向整流器(用于快速整流器钾电流,称为IK(FR)),类似于心肌中描述的钾电流,另一种是瞬态A电流(IA)。 3. IK(FR)的激活和失活速率与电压有关。激活的时间常数适合n4动力学,从3.5毫秒(-20毫伏)降至1.1毫秒(60毫伏)。灭活具有双指数的时间过程,其电压无关的时间常数在10至50 mV之间为0.3 s(次要分量)和3.0 s(主要分量)。 IK(FR)在-40 mV以上被激活,V1 / 2(半最大激活时的膜电位)为14 +/- 2 mV,斜率因子为-17 +/- 1 mV,达到了电导(非最大) 60 mV时为10.8 +/- 1.7 nS。稳态失活的斜率因子为11 +/- 1 mV。 4. IK(FR)对K +具有高度选择性(PNa / PK = 0.002)。四乙铵(TEA)可逆地降低IK(FR)(IC50 = 20 mM),而10 mM处的4-氨基吡啶(4-AP)作用很小。 30 mM TEA中的剩余电流与对照条件下的电流相似,这表明TEA降低了IK(FR),而不显示出额外的TEA耐性电流。 5. IA激活的速率与电压有关,其到达峰值的时间从8.5 ms(在-40 mV时)下降到3.6 ms(在60 mV时)。灭活具有双指数的时间过程,具有与电压有关和与电压无关的时间常数。这两个分量的幅度相似。 IA在-60 mV以上激活,在20 mV以上达到3.6 +/- 0.4 nS的最大电导。 -10 mV以上,稳态失活完成。失活的开始速率(-40 mV)和失活的恢复速率(-100 mV)相似,时间常数分别为39 +/- 5和41 +/- 9 ms。 6.在SCN中测​​试的每个神经元以及整个核的所有位置均发现IK(FR)和IA。讨论了这些电流的可能功能,特别是关于SCN中点火速率的昼夜节律。

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