Low-frequency neuromuscular depression is a consequence of a reduction in nerve terminal Ca2+ currents at mammalian motor nerve endings.
Low-frequency neuromuscular depression is a consequence of a reduction in nerve terminal Ca2+ currents at mammalian motor nerve endings.
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低频神经肌肉抑制是哺乳动物运动神经末梢神经末梢 Ca2 电流减少的结果。
DOI：
10.1097/aln.0b013e31829083d8
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发表时间：
2013
期刊：
影响因子：
8.8
通讯作者：
Silinsky,EugeneM
中科院分区：
文献类型：
--
作者：
Silinsky,EugeneM
研究背景低频神经刺激时随意肌收缩的减少在临床上被用来评估神经肌肉阻滞的类型和程度。这种抑郁症的机制是未知的。Methodssimultaneouselectrical measurements神经递质释放和prejunctionalCa 2+电流的小鼠神经肌肉接头进行评估的假设，减少神经末梢Ca 2+电流是负责低频depress.ResultsUnder条件下，通常用于测量在神经肌肉接头的Ca 2+电流，将神经刺激的频率从0.017短暂增加到0.1-1 Hz，同时引起神经递质乙酰胆碱的释放减少到对照的52.2±4.4%和Ca 2+电流峰值减少到对照的75.4± 2.0（P< 0.001，对于两种测量，n= 5次实验，所有数据的平均值土SEM）。在用于四串监测的条件下（4个刺激，2 Hz），在第一和第四刺激之间，神经递质释放下降至对照的42.0±1.0%，并且Ca 2+电流峰值下降至对照的75.8±3.3%（P< 0.001，对于两种测量n= 7个实验）。抑郁症的乙酰胆碱释放过程中列车的四个协议也发生在没有neuromuscular-blocking drugs.DiscussionThe结果表明，在列车的四个监测神经肌肉抑郁症是由于神经末梢钙电流下降，从而减少乙酰胆碱的释放。由于类似的过程可能在更高的刺激频率下起作用，因此可以使用拮抗Ca 2+电流下降的药物来治疗神经肌肉抑制可能使人衰弱的病症。
BackgroundThe decline in voluntary muscle contraction during low-frequency nerve stimulation is used clinically to assess the type and degree of neuromuscular block. The mechanism underlying this depression is unknown.MethodsSimultaneous electrophysiological measurements of neurotransmitter release and prejunctional Ca2+ currents were made at mouse neuromuscular junctions to evaluate the hypothesis that decreases in nerve terminal Ca2+ currents are responsible for low-frequency depression.ResultsUnder conditions generally used to measure Ca2+ currents at the neuromuscular junction, increasing the frequency of nerve stimulation briefly from 0.017 to 0.1–1 Hz caused a simultaneous reduction in the release of the neurotransmitter acetylcholine to 52.2±4.4% of control and the Ca2+ current peak to 75.4±2.0% of control (P< 0.001, n= 5 experiments for both measurements, mean±SEM for all data). In conditions used for train-of-four monitoring (4 stimuli, 2 Hz), neurotransmitter release declined to 42.0±1.0% of control and the Ca2+ current peak declined to 75.8±3.3% of control between the first and fourth stimulus (P< 0.001, n= 7 experiments for both measurements). Depression in acetylcholine release during train-of-four protocols also occurred in the absence of neuromuscular-blocking drugs.DiscussionThe results demonstrate that neuromuscular depression during train-of-four monitoring is due to a decline in nerve terminal Ca2+ currents, hence reducing the release of acetylcholine. As similar processes may come into play at higher stimulation frequencies, agents that antagonize the decline in Ca2+ currents could be used to treat conditions in which neuromuscular depression can be debilitating.