Relationship between repetitive firing and afterhyperpolarizations in human neocortical neurons.

Relationship between repetitive firing and afterhyperpolarizations in human neocortical neurons.
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人类新皮质神经元重复放电与后超极化之间的关系。

DOI:
10.1152/jn.1992.67.2.350
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发表时间:
1992
影响因子:
2.5
通讯作者:
Foehring,RC
Foehring,RC
中科院分区:
医学3区
文献类型:
--
作者:
Lorenzon,NM;Foehring,RC

文献摘要

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1.人类新皮层神经元对长时间去极化电流注入的反应是重复放电。在这些细胞中,平均放电频率与注入电流之间的关系(f-I斜率)呈线性或双线性。平均稳态f-I斜率(1秒放电事件最后500 ms的平均值)为57.8 Hz/nA。瞬时放电率随时间的推移而下降,在1秒的恒定电流注入(尖峰频率适应)。此外,人类神经元表现出适应性反应的1秒电流刺激每2秒重复。2.后超极化(Afterhyperpolarizations,AHPs)反映动作电位后的活性离子电导。我们在体外切片制备中使用细胞内记录和药理学操作研究了AHPs,以1)深入了解AHPs的离子机制和2)阐明潜在电流在人类皮层神经元功能行为中的作用。3.我们在人类新皮层神经元的基础上,他们的时间进程:快,中,慢的AHPs进行了分类。AHPs的幅度依赖于刺激强度和持续时间,尖峰的数量和频率,以及膜电位。4.快速AHP具有-65 mV的逆转电位,并且在细胞外的Co 2+、四乙基铵(TEA)或4-氨基吡啶以及细胞内的TEA或CsCl中被消除。这些操作也导致了尖峰宽度的增加。5.中等AHP的逆转电位为-90至-93 mV(从平均静息电位超极化22-24 mV)。该AHP被Co 2+、apamin、tubocurare、毒蕈碱、去甲肾上腺素(NE)和5-羟色胺(5-HT)降低。药理学操作表明,中等AHP部分由1)Ca依赖性K+电流和2)时间依赖性异常整流器(IH)产生。6.缓慢的AHP在-83至-87 mV(从平均静息电位超极化14-18 mV)时逆转。该AHP被Co 2+、毒蕈碱、NE和5-HT减弱。慢AHP的药理学表明,具有缓慢动力学的Ca依赖性K+电流有助于该AHP。7.快速AHP中涉及的电流在锋电位复极、重复放电过程中锋电位间期的控制和猝发放电的预防中是重要的。电流的基础上的中,慢AHPs的影响,在重复发射和产生尖峰频率适应和习惯化的峰间期。
1. Human neocortical neurons fire repetitively in response to long depolarizing current injections. The slope of the relationship between average firing frequency and injected current (f-I slope) was linear or bilinear in these cells. The mean steady-state f-I slope (average of the last 500 ms of a 1-s firing episode) was 57.8 Hz/nA. The instantaneous firing rate decreased with time during a 1-s constant-current injection (spike frequency adaptation). Also, human neurons exhibited habituation in response to a 1-s current stimulus repeated every 2 s. 2. Afterhyperpolarizations (AHPs) reflect the active ionic conductances after action potentials. We studied AHPs with the use of intracellular recordings and pharmacological manipulations in the in vitro slice preparation to 1) gain insight into the ionic mechanisms underlying the AHPs and 2) elucidate the role that the underlying currents play in the functional behavior of human cortical neurons. 3. We have classified three AHPs in human neocortical neurons on the basis of their time courses: fast, medium, and slow. The amplitude of the AHPs was dependent on stimulus intensity and duration, number and frequency of spikes, and membrane potential. 4. The fast AHP had a reversal potential of -65 mV and was eliminated in extracellular Co2+, tetraethylammonium (TEA) or 4-aminopyridine, and intracellular TEA or CsCl. These manipulations also caused an increase in spike width. 5. The medium AHP had a reversal potential of -90 to -93 mV (22-24 mV hyperpolarized from mean resting potential). This AHP was reduced by Co2+, apamin, tubocurare, muscarine, norepinephrine (NE), and serotonin (5-HT). Pharmacological manipulations suggest that the medium AHP is produced in part by 1) a Ca-dependent K+ current and 2) a time-dependent anomalous rectifier (IH). 6. The slow AHP reversed at -83 to -87 mV (14-18 mV hyperpolarized from mean resting potential). This AHP was diminished by Co2+, muscarine, NE, and 5-HT. The pharmacology of the slow AHP suggests that a Ca-dependent K+ current with slow kinetics contributes to this AHP. 7. The currents involved in the fast AHP are important in spike repolarization, control of interspike interval during repetitive firing, and prevention of burst firing. Currents underlying the medium and slow AHPs influence the interspike interval during repetitive firing and produce spike frequency adaptation and habituation.