Endothelin-1 raises excitability and reduces potassium currents in sensory neurons.

Endothelin-1 raises excitability and reduces potassium currents in sensory neurons.
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内皮素-1提高兴奋性并减少感觉神经元中的钾电流。

DOI:
10.1016/j.brainresbull.2009.04.012
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发表时间:
2009-08-14
影响因子:
3.8
通讯作者:
Strichartz, Gary
Strichartz, Gary
中科院分区:
医学3区
文献类型:
--
作者:
Feng, Bihua;Strichartz, Gary

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从大鼠背根神经节急性分离的感觉神经元暴露于内皮素-1(ET-1,50 nM),导致刺激电流线性斜坡引起的动作电位数量增加。ET-1处理后5分钟内,这些变化完全,ET-1去除后5-10分钟内不逆转。ET-1暴露既不改变静息电位,也不改变第一或第二动作电位的阈值电位,也不改变它们的上升或衰减速率,但在电流斜坡期间在第一和第二动作电位之前发生的缓慢去极化增加约1.5倍。50%的ET-1。在全细胞电压钳下测量的延迟整流型K+电流(IK)在暴露于ET-1期间被抑制约30%。稳态IK的电压依赖性门控和电流动力学未被ET-1改变,留下的唯一效应是可用通道数量的下降。IK仅在Isolectin B4阳性细胞中受到ET-1的影响,这表明在增强这类伤害性神经元的冲动活动中可能存在选择性作用。这种IK的减少将增强先前报道的河豚毒素抗性Na+通道门控在这些神经元中的负移的兴奋性诱导作用。
Exposure to endothelin-1 (ET-1, 50nM) of sensory neurons, acutely isolated from rat dorsal root ganglia, results in an increase in the number of action potentials elicited by a linear ramp of stimulating current. The changes are complete in 5 minutes after ET-1 treatment and do not reverse in 5-10 minutes after ET-1’s removal. Neither the resting potential, nor the threshold potential for the first or second action potentials, nor their rate of rise or decay, are changed by ET-1 exposure, but the slow depolarizations which occur before the first and second action potentials during the current ramp are increased by ca. 50% by ET-1. The delayed rectifier type of K+ currents (IK), measured under whole-cell voltage clamp, are depressed by ~30% during such exposure to ET-1. The voltage-dependent gating of steady-state IK and the current kinetics are unchanged by ET-1, leaving the sole effect as a drop in the number of available channels. IK is affected by ET-1 only in Isolectin B4-positive cells, suggesting that there may be a selective action in enhancing impulse activity on this class of nociceptive neuron. This decrease in IK will potentiate the excitability-inducing actions of the previously reported negative shift in tetrodotoxin-resistant Na+ channel gating in such neurons.
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