Distinct roles for IT and IH in controlling the frequency and timing of rebound spike responses
Distinct roles for IT and IH in controlling the frequency and timing of rebound spike responses
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DOI：
10.1113/jphysiol.2011.215632
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发表时间：
2011-11-01
影响因子：
5.5
通讯作者：
Turner, Ray W.
中科院分区：
文献类型：
--
作者：
Engbers, Jordan D. T.;Anderson, Dustin;Turner, Ray W.
神经元在抑制性突触输入后产生反弹爆发的能力依赖于以独特方式响应超极化的离子通道。由T型钙通道（I-T）和超极化激活的HCN通道（I-H）提供的内向电流在超极化时增加可用性，允许在一段时间的抑制后出现反弹去极化。虽然反弹反应早已被确认在深小脑核（DCN）神经元，在何种程度上I-T和I-H有助于反弹尖峰输出以下生理水平的膜超极化的实际程度还没有明确的建立。目前的研究使用记录和模拟的大直径细胞的体外大鼠DCN切片制备，以确定的作用，I-T和I-H的反弹反应。我们发现，生理水平的超极化，使只有一小部分的总I-T和I-H可用，但这些都足以作出重大贡献的反弹反应。至少50%的早期反弹尖峰频率增加是由I-T介导的去极化产生的。当膜从超极化状态返回到静息水平时，I-H在降低时间常数方面提供了额外的频率增加，从而降低了I-T失活的程度。一个I-H介导的去极化创建一个反向电压第一尖峰潜伏期的关系，并产生了35%的反弹的第一尖峰潜伏期的精度增加。因此，I-T和I-H可以被生理相关刺激激活，并且在反弹反应的频率、时间和精确度方面具有不同的作用。
The ability for neurons to generate rebound bursts following inhibitory synaptic input relies on ion channels that respond in a unique fashion to hyperpolarization. Inward currents provided by T-type calcium channels (I-T) and hyperpolarization-activated HCN channels (I-H) increase in availability upon hyperpolarization, allowing for a rebound depolarization after a period of inhibition. Although rebound responses have long been recognized in deep cerebellar nuclear (DCN) neurons, the actual extent to which I-T and I-H contribute to rebound spike output following physiological levels of membrane hyperpolarization has not been clearly established. The current study used recordings and simulations of large diameter cells of the in vitro rat DCN slice preparation to define the roles for I-T and I-H in a rebound response. We find that physiological levels of hyperpolarization make only small proportions of the total I-T and I-H available, but that these are sufficient to make substantial contributions to a rebound response. At least 50% of the early phase of the rebound spike frequency increase is generated by an I-T-mediated depolarization. An additional frequency increase is provided by I-H in reducing the time constant and thus the extent of I-T inactivation as the membrane returns from a hyperpolarized state to the resting level. An I-H-mediated depolarization creates an inverse voltage-first spike latency relationship and produces a 35% increase in the precision of the first spike latency of a rebound. I-T and I-H can thus be activated by physiologically relevant stimuli and have distinct roles in the frequency, timing and precision of rebound responses.