Identification and modelling of fast and slow Ih current components in vestibular ganglion neurons.
Identification and modelling of fast and slow Ih current components in vestibular ganglion neurons.
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DOI：
10.1111/ejn.13021
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发表时间：
2015-11
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影响因子：
--
通讯作者：
Graham BP
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文献类型：
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作者：
Michel CB;Azevedo Coste C;Desmadryl G;Puel JL;Bourien J;Graham BP
先前的实验数据表明，内耳中的超极化激活阳离子（I h）电流由两种成分[不同的超极化激活环核苷酸门控（HCN）亚基]组成，这两种成分不可能完全分离。为了确认前庭神经节神经元中这两个组件的存在，我们应用了一种参数识别算法，该算法能够从实验数据中区分这两个组件的参数。使用模拟数据，我们已经表明，该算法能够比经典方法更准确地识别非失活离子通道的两个群体的参数。此外，该算法被证明是不敏感的关键参数的变化。然后，我们将此算法应用于小鼠前庭神经节神经元的I h电流记录。该算法显示存在高压激活的慢分量和低压激活的快分量。最后，这两个I h组件的电生理学意义进行了测试，分别在计算前庭神经节神经元模型（持续和短暂的），在控制情况下，并在cAMP的存在下，细胞内的环核苷酸，调节HCN通道活性。结果表明，第一，快速和缓慢的组件调制不同的动作电位兴奋性和兴奋性突触后电位在持续和短暂的前庭神经元，第二，快速和缓慢的组件，在控制情况下，提供不同的信息特性的刺激和这种信息的调制后cAMP显着修改。
Previous experimental data indicates the hyperpolarization‐activated cation (I h) current, in the inner ear, consists of two components [different hyperpolarization‐activated cyclic nucleotide‐gated (HCN) subunits] which are impossible to pharmacologically isolate. To confirm the presence of these two components in vestibular ganglion neurons we have applied a parameter identification algorithm which is able to discriminate the parameters of the two components from experimental data. Using simulated data we have shown that this algorithm is able to identify the parameters of two populations of non‐inactivated ionic channels more accurately than a classical method. Moreover, the algorithm was demonstrated to be insensitive to the key parameter variations. We then applied this algorithm to I h current recordings from mouse vestibular ganglion neurons. The algorithm revealed the presence of a high‐voltage‐activated slow component and a low‐voltage‐activated fast component. Finally, the electrophysiological significance of these two I h components was tested individually in computational vestibular ganglion neuron models (sustained and transient), in the control case and in the presence of cAMP, an intracellular cyclic nucleotide that modulates HCN channel activity. The results suggest that, first, the fast and slow components modulate differently the action potential excitability and the excitatory postsynaptic potentials in both sustained and transient vestibular neurons and, second, the fast and slow components, in the control case, provide different information about characteristics of the stimulation and this information is significantly modified after modulation by cAMP.