Neuroscience Research Australia, Sydney, NSW 2031, Australia.
Eur J Neurosci. 2013 Mar;37(6):876-90. doi: 10.1111/ejn.12116. Epub 2013 Jan 10.
Giant cells of the cochlear nucleus are thought to integrate multimodal sensory inputs and participate in monaural sound source localization. Our aim was to explore the significance of a hyperpolarization-activated current in determining the activity of giant neurones in slices prepared from 10 to 14-day-old rats. When subjected to hyperpolarizing stimuli, giant cells produced a 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyridinium chloride (ZD7288)-sensitive inward current with a reversal potential and half-activation voltage of -36 and -88 mV, respectively. Consequently, the current was identified as the hyperpolarization-activated non-specific cationic current (Ih ). At the resting membrane potential, 3.5% of the maximum Ih conductance was available. Immunohistochemistry experiments suggested that hyperpolarization-activated, cyclic nucleotide-gated, cation non-selective (HCN)1, HCN2, and HCN4 subunits contribute to the assembly of the functional channels. Inhibition of Ih hyperpolarized the membrane by 6 mV and impeded spontaneous firing. The frequencies of spontaneous inhibitory and excitatory postsynaptic currents reaching the giant cell bodies were reduced but no significant change was observed when evoked postsynaptic currents were recorded. Giant cells are affected by biphasic postsynaptic currents consisting of an excitatory and a subsequent inhibitory component. Inhibition of Ih reduced the frequency of these biphasic events by 65% and increased the decay time constants of the inhibitory component. We conclude that Ih adjusts the resting membrane potential, contributes to spontaneous action potential firing, and may participate in the dendritic integration of the synaptic inputs of the giant neurones. Because its amplitude was higher in young than in adult rats, Ih of the giant cells may be especially important during the postnatal maturation of the auditory system.
耳蜗核中的巨大细胞被认为整合多模态感觉输入，并参与单耳声源定位。我们的目的是探索超极化激活电流在决定 10 至 14 天大鼠脑片制备中巨大神经元活性中的作用。当受到超极化刺激时，巨大细胞产生一种 4-(N-乙基-N-苯基氨基)-1,2-二甲基-6-(甲氨基)吡啶氯化物 (ZD7288) 敏感内向电流，反转电位和半激活电压分别为-36 和-88 mV。因此，该电流被鉴定为超极化激活非特异性阳离子电流 (Ih)。在静息膜电位下，最大 Ih 电导的 3.5%可用。免疫组织化学实验表明，超极化激活、环核苷酸门控、阳离子非选择性 (HCN)1、HCN2 和 HCN4 亚基有助于功能性通道的组装。Ih 抑制使膜超极化 6 mV，并阻碍自发放电。到达巨大细胞体的自发性抑制和兴奋性突触后电流的频率降低，但当记录到诱发的突触后电流时，没有观察到明显变化。巨大细胞受到由兴奋性和随后的抑制性组成的双相突触后电流的影响。Ih 抑制使这些双相事件的频率降低 65%，并增加抑制性成分的衰减时间常数。我们得出结论，Ih 调节静息膜电位，有助于自发性动作电位放电，并可能参与巨大神经元突触输入的树突整合。由于其在幼年大鼠中的幅度高于成年大鼠，因此巨大细胞的 Ih 在听觉系统的出生后成熟过程中可能尤为重要。
