Heterogeneous intrinsic excitability of murine spiral ganglion neurons is determined by Kv1 and HCN channels.
Heterogeneous intrinsic excitability of murine spiral ganglion neurons is determined by Kv1 and HCN channels.
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DOI：
10.1016/j.neuroscience.2013.10.065
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发表时间：
2014-01-17
期刊：
影响因子：
3.3
通讯作者：
Davis RL
中科院分区：
文献类型：
--
作者：
Liu Q;Lee E;Davis RL
螺旋神经节主要通过一类 I 型神经元传递传入听觉信息，这些神经元接收来自内毛细胞 (IHC) 感觉受体的信号。与其他系统一样，这些听觉初级传入神经的电生理特征具有显着的多样性。与这些观察结果一致，当在与外周和中枢目标分离的神经元外植体中评估听觉初级传入神经时，发现单个神经元的内源性电生理特征明显异质。这种异质性的一个方面（在整个神经节中都很明显）是通过电压阈值测量评估的其广泛的兴奋性。因此，虽然基部神经元的电压阈值与顶端和中间神经元显着不同，但每个区域都显示出明显较宽的值范围。为了确定这些神经元的静息膜电位 (RMP) 是否与阈值分布相关，并确定神经节异质神经元兴奋性背后的离子通道调节元件，在体外对出生后 (P5-8) 的小鼠螺旋神经节神经元进行膜片钳记录。我们发现 RMP 反映了音调阈值分布，并在每个耳蜗位置贡献了额外水平的异质性。药理学实验进一步表明，阈值和RMP通过Kv1电流耦合，这对两个电生理参数具有双重影响。然而，超极化激活的阳离子通道 (HCN) 主要通过影响 RMP 而不改变阈值水平来解耦这两个过程。因此，除了机械和突触的专门化之外，离子通道对内在膜特性的调节使螺旋神经节神经元具有不同的兴奋性水平，这一特征有助于初级听觉传入的多样性。
The spiral ganglion conveys afferent auditory information predominantly through a single class of type I neurons that receive signals from inner hair cell (IHC) sensory receptors. These auditory primary afferents, like in other systems possess a marked diversity in their electrophysiological features. Consistent with these observations, when the auditory primary afferents were assessed in neuronal explants separated from their peripheral and central targets it was found that individual neurons were markedly heterogeneous in their endogenous electrophysiological features. One aspect of this heterogeneity, obvious throughout the ganglion, was their wide range of excitability as assessed by voltage threshold measurements. Thus, while neurons in the base differed significantly from apical and middle neurons in their voltage thresholds, each region showed distinctly wide ranges of values. To determine whether the resting membrane potentials (RMP) of these neurons correlate with the threshold distribution and to identify the ion channel regulatory elements underlying heterogeneous neuronal excitability in the ganglion, patch-clamp recordings were made from postnatal day (P5-8) murine spiral ganglion neurons in vitro. We found that RMP mirrored the tonotopic threshold distribution, and contributed an additional level of heterogeneity in each cochlear location. Pharmacological experiments further indicated that threshold and RMP was coupled through the Kv1 current, which had a dual impact on both electrophysiological parameters. Whereas, hyperpolarization-activated cationic channels (HCN) decoupled these two processes by primarily affecting RMP without altering threshold level. Thus, beyond mechanical and synaptic specializations, ion channel regulation of intrinsic membrane properties imbues spiral ganglion neurons with different excitability levels, a feature that contributes to primary auditory afferent diversity.