Mechanisms of Sustained High Firing Rates in Two Classes of Vestibular Nucleus Neurons: Differential Contributions of Resurgent Na, Kv3, and BK Currents

Mechanisms of Sustained High Firing Rates in Two Classes of Vestibular Nucleus Neurons: Differential Contributions of Resurgent Na, Kv3, and BK Currents
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DOI:
10.1152/jn.00378.2010
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发表时间:
2010-09-01
影响因子:
2.5
通讯作者:
du Lac, Sascha
du Lac, Sascha
中科院分区:
医学3区
文献类型:
--
作者:
Gittis, Aryn H.;Moghadam, Setareh H.;du Lac, Sascha

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Gittis AH,Moghadam SH,du Lac S.两类前庭神经核神经元持续高放电率的机制:复苏Na,Kv 3和BK电流的差异贡献。J Neurophysiol 104:1625-1634,2010.首次发表于2010年6月30日; doi:10.1152/jn.00378.2010。为了以高速率放电,神经元表达离子电流,这些离子电流共同作用,通过确保钠通道在每个动作电位后不久可用于激活来最小化不应期。前庭核神经元围绕高基线放电率工作,并以高达数百Hz的放电率双向调制来编码信息。为了确定使这些神经元能够维持高速率放电的机制,通过使用动作电位钳技术在从转基因小鼠急性分离的前庭核神经元中测量放电期间的离子电流。虽然来自YFP-16线的神经元以高于来自GIN线的那些的速率放电,但是两类神经元表达Kv 3和BK电流以及瞬时和复苏Na电流。在放电最快的神经元中,Kv 3电流在所有放电速率下主导复极,并通过将Na通道从开放状态快速转换为关闭状态来最小化Na通道失活。在慢放电神经元,BK电流占主导地位的复极在最高的放电率和钠通道的可用性保护的复苏阻断机制。跨神经元的Kv 3电流密度的定量差异和荧光化学检测的Kv 3亚基表达的定性差异可以解释细胞类别内和跨细胞类别的放电范围的差异。这些结果表明,两个神经元群体的发散放电特性是如何通过至少三个离子电流的相互作用而产生的。
Gittis AH, Moghadam SH, du Lac S. Mechanisms of sustained high firing rates in two classes of vestibular nucleus neurons: differential contributions of resurgent Na, Kv3, and BK currents. J Neurophysiol 104: 1625-1634, 2010. First published June 30, 2010; doi: 10.1152/jn.00378.2010. To fire at high rates, neurons express ionic currents that work together to minimize refractory periods by ensuring that sodium channels are available for activation shortly after each action potential. Vestibular nucleus neurons operate around high baseline firing rates and encode information with bidirectional modulation of firing rates up to several hundred Hz. To determine the mechanisms that enable these neurons to sustain firing at high rates, ionic currents were measured during firing by using the action potential clamp technique in vestibular nucleus neurons acutely dissociated from transgenic mice. Although neurons from the YFP-16 line fire at rates higher than those from the GIN line, both classes of neurons express Kv3 and BK currents as well as both transient and resurgent Na currents. In the fastest firing neurons, Kv3 currents dominated repolarization at all firing rates and minimized Na channel inactivation by rapidly transitioning Na channels from the open to the closed state. In slower firing neurons, BK currents dominated repolarization at the highest firing rates and sodium channel availability was protected by a resurgent blocking mechanism. Quantitative differences in Kv3 current density across neurons and qualitative differences in immunohistochemically detected expression of Kv3 subunits could account for the difference in firing range within and across cell classes. These results demonstrate how divergent firing properties of two neuronal populations arise through the interplay of at least three ionic currents.