Cao Xiao-Jie, Oertel Donata
Department of Neuroscience, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA.
Department of Neuroscience, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA.
Hear Res. 2017 Mar;345:57-68. doi: 10.1016/j.heares.2017.01.001. Epub 2017 Jan 5.
Low-voltage-activated K (g) and hyperpolarization-activated mixed cation conductances (g) mediate currents, I and I, through channels of the Kv1 (KCNA) and HCN families respectively and give auditory neurons the temporal precision required for signaling information about the onset, fine structure, and time of arrival of sounds. Being partially activated at rest, g and g contribute to the resting potential and shape responses to even small subthreshold synaptic currents. Resting g and g also affect the coupling of somatic depolarization with the generation of action potentials. To learn how these important conductances are regulated we have investigated how genetic perturbations affect their expression in octopus cells of the ventral cochlear nucleus (VCN). We report five new findings: First, the magnitude of g and g varied over more than two-fold between wild type strains of mice. Second, average resting potentials are not different in different strains of mice even in the face of large differences in average g and g. Third, I has two components, one being α-dendrotoxin (α-DTX)-sensitive and partially inactivating and the other being α-DTX-insensitive, tetraethylammonium (TEA)-sensitive, and non-inactivating. Fourth, the loss of Kv1.1 results in diminution of the α-DTX-sensitive I, and compensatory increased expression of an α-DTX-insensitive, tetraethylammonium (TEA)-sensitive I. Fifth, I and I are balanced at the resting potential in all wild type and mutant octopus cells even when resting potentials vary in individual cells over nearly 10 mV, indicating that the resting potential influences the expression of g and g. The independence of resting potentials on g and g shows that g and g do not, over days or weeks, determine the resting potential but rather that the resting potential plays a role in regulating the magnitude of either or both g and g.
低电压激活的钾离子通道（g）和超极化激活的混合阳离子电导（g）分别通过Kv1（KCNA）家族和HCN家族的通道介导电流I和电流I，赋予听觉神经元传递有关声音起始、精细结构和到达时间信息所需的时间精度。g和g在静息时部分激活，有助于静息电位，并塑造对即使很小的阈下突触电流的反应。静息时的g和g也会影响体细胞去极化与动作电位产生之间的耦合。为了了解这些重要的电导是如何被调节的，我们研究了基因扰动如何影响它们在腹侧耳蜗核（VCN）章鱼细胞中的表达。我们报告了五个新发现：第一，g和g的大小在野生型小鼠品系之间变化超过两倍。第二，即使平均g和g存在很大差异，不同品系小鼠的平均静息电位也没有差异。第三，电流I有两个成分，一个对α-树突毒素（α-DTX）敏感且部分失活，另一个对α-DTX不敏感、对四乙铵（TEA）敏感且不失活。第四，Kv1.1的缺失导致对α-DTX敏感的电流I减少，以及对α-DTX不敏感、对四乙铵（TEA）敏感的电流I的代偿性表达增加。第五，在所有野生型和突变型章鱼细胞中，即使单个细胞的静息电位变化近10 mV，电流I和电流I在静息电位时也是平衡的，这表明静息电位会影响g和g的表达。静息电位对g和g的独立性表明，g和g在数天或数周内不会决定静息电位，而是静息电位在调节g和g中的一个或两个的大小方面发挥作用。
