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首页> 外文期刊>Journal of Neurophysiology >High-frequency stimulation produces a transient blockade of voltage-gated currents in subthalamic neurons.
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High-frequency stimulation produces a transient blockade of voltage-gated currents in subthalamic neurons.

机译:高频刺激在丘脑下神经元中产生电压门控电流的瞬时阻断。

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The effect of high-frequency stimulation (HFS) of the subthalamic nucleus (STN) was analyzed with patch-clamp techniques (whole cell configuration, current- and voltage-clamp modes) in rat STN slices in vitro. A brief tetanus, consisting of 100-micros bipolar stimuli at a frequency of 100--250 Hz during 1 min, produced a full blockade of ongoing STN activity whether it was in the tonic or bursting mode. This HFS-induced silence lasted around 6 min after the end of stimulation, was frequency dependent, could be repeated without alteration, and was not synaptically induced as it was still observed in the presence of blockers of ionotropic GABA and glutamate receptors or in the presence of cobalt at a concentration (2 mM) that blocks voltage-gated Ca(2+) channels and synaptic transmission. During HFS-induced silence, the following alterations were observed: the persistent Na(+) current (I(NaP)) was totally blocked (by 99%), the Ca(2+)-mediated responses were strongly reduced including the posthyperpolarization rebound (-62% in amplitude) and the plateau potential (-76% in duration), suggesting that T- and L-type Ca(2+) currents are transiently depressed by HFS, whereas the Cs(+)-sensitive, hyperpolarization-activated cationic current (I(h)) was little affected. Thus a high-frequency tetanus produces a blockade of the spontaneous activities of STN neurons as a result of a strong depression of intrinsic voltage-gated currents underlying single-spike and bursting modes of discharge. These effects of HFS, which are completely independent of synaptic transmission, provide a mechanism for interrupting ongoing activities of STN neurons.
机译:使用膜片钳技术(整个细胞配置,电流和电压钳模式)在体外大鼠STN切片中分析了丘脑底核(STN)的高频刺激(HFS)的效果。短暂的破伤风由100微米的双极刺激物组成,在1分钟内以100--250 Hz的频率发生,无论是在强直性还是爆发性模式下,都对正在进行的STN活动产生了完全的阻断。这种HFS诱导的沉默在刺激结束后持续约6分钟,它是频率依赖性的,可以重复而没有改变,并且不是突触地诱导的,因为在存在离子型GABA和谷氨酸受体阻滞剂的情况下或存在下仍观察到浓度(2 mM)的钴可阻止电压门控的Ca(2+)通道和突触传递。在HFS诱导的沉默期间,观察到以下变化:持久性Na(+)电流(I(NaP))被完全阻止(99%),Ca(2+)介导的反应被强烈降低,包括超极化后的反弹(幅度为-62%)和平稳电位(持续时间为-76%),表明T型和L型Ca(2+)电流被HFS瞬时抑制,而Cs(+)敏感,超极化-活化阳离子电流(I(h))几乎没有受到影响。因此,由于在单尖峰放电模式和突发放电模式下固有的电压门控电流的强烈抑制,高频破伤风会阻止STN神经元的自发活动。完全独立于突触传递的HFS的这些作用提供了一种中断STN神经元正在进行的活动的机制。

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