Physiological and theoretical analysis of K+ currents controlling discharge in neonatal rat mesencephalic trigeminal neurons.

Physiological and theoretical analysis of K+ currents controlling discharge in neonatal rat mesencephalic trigeminal neurons.
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DOI:
10.1152/jn.1997.77.2.537
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发表时间:
1997-02
影响因子:
2.5
通讯作者:
C. A. D. Negro;S. H. Chandler
C. A. D. Negro;S. H. Chandler
中科院分区:
医学3区
文献类型:
--
作者:
C. A. D. Negro;S. H. Chandler

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用红外视频显微镜对新生大鼠脑干薄片中的中脑三叉神经感觉(MES-5)神经元进行全细胞电压和电流钳记录。这些细胞表现出对去极化电流注入方案的尖峰放电反应的适应,其持续时间随保持电位的不同而不同(-50 mV对-65 mV)。在-50 mV的膜反应前,可诱发多个动作电位,而在-65 mV的膜反应中,仅诱发单个动作电位。对于类似的方案,应用K+通道阻滞剂4-氨基吡啶(4-AP)(50微米至2 mM)可引起持续的重复峰电位,而四乙基铵(TEA)(10~30 mM)不能引起重复峰电位。在电压钳中,施加4-AP(100微米)显示持续的外向电流(I4-AP),其活动范围在-60 mV到-30 mV之间。I4-AP负责抑制持续重复的尖峰行为,在正常情况下产生调节。在电压钳中应用TEA后,持续外向电流为-40 mV。A型电流的典型特征是两种瞬时外向电流(TOC):对4-AP不敏感的快速TOC和对4-AP(500微米)敏感的慢TOC(TOC-S)。钙离子依赖的外向电流被激活到-30 mV。根据我们的电压钳记录组装了MES 5神经元的数学模型,以模拟膜兴奋过程中外向电流的动态相互作用。我们认为在MES5神经元中,4-AP敏感电流ITOC-S和I4-AP决定了棘波串的时程。特别是,非失活的I4-AP决定了细胞是否表现出持续的重复放电或适应去极化电流。神经递质对这一电流的调制或静息膜电位的调制可能会改变MES 5神经元的输出特性,因此这些电流的特性必须被纳入我们目前对这些细胞如何参与塑造口腔运动模式生成的理解中。
Whole cell voltage- and current-clamp recordings were obtained from mesencephalic trigeminal sensory (Mes 5) neurons identified visually in thin brain stem slices of neonatal rats with the use of infrared video microscopy. These cells exhibited accommodation in spike discharge responses to depolarizing current injection protocols whose duration differed as a function of holding potential (-50 vs. -65 mV). Several spikes were elicited before the membrane response accommodated from -50 mV, whereas from -65 mV only single action potentials were evoked. In response to similar protocols, application of the K+ channel blocker 4-aminopyridine (4-AP) (50 microM to 2 mM) caused sustained repetitive spiking whereas tetraethylammonium (TEA) (10-30 mM) did not cause repetitive spiking. In voltage clamp, 4-AP application (100 microM) revealed a sustained outward current (I4-AP) that was active between -60 and -30 mV. I4-AP was responsible for suppressing sustained repetitive spiking behavior, producing accommodation under normal circumstances. TEA application in voltage clamp revealed a sustained outward current evoked positive to -40 mV. Two transient outward currents (TOCs) were identified by prepulse protocols typically used to characterize A-type currents: a 4-AP-insensitive fast TOC, and a slow TOC (ITOC-S) sensitive to 4-AP (> 500 microM). A Ca(2+)-dependent outward current that activated positive to -30 mV was also characterized. A mathematical model of a Mes 5 neuron was assembled from our voltage-clamp records to simulate the dynamic interaction of outward currents during membrane excitation. We conclude that in Mes 5 neurons, the 4-AP-sensitive currents ITOC-S and I4-AP determine the duration of spike trains. In particular, the noninactivating I4-AP determines whether cells exhibit sustained repetitive discharge or accommodate in response to depolarizing current. Neurotransmitter modulation of this current or modulation of the resting membrane potential could modify the output properties of Mes 5 neurons, and therefore the properties of these currents must be incorporated into our current understanding of how these cells contribute to shaping oral-motor pattern generation.