Hyperpolarization-activated, mixed-cation current (Ih) in octopus cells of the mammalian cochlear nucleus

Hyperpolarization-activated, mixed-cation current (Ih) in octopus cells of the mammalian cochlear nucleus
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DOI:
10.1152/jn.2000.84.2.806
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发表时间:
2000-08-01
影响因子:
2.5
通讯作者:
Oertel, D
Oertel, D
中科院分区:
医学3区
文献类型:
--
作者:
Bal, R;Oertel, D

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哺乳动物后腹侧耳蜗核中的章鱼细胞检测听觉神经纤维群体中同步放电的一致性,并以很高的时间精度传达该一致性的时间。电流钳中的早期记录表明,两个电导有助于低输入电阻,因此有助于章鱼细胞精确编码时间的能力,低阈值K+电导和超极化激活的混合阳离子电导g(h)。本实验描述了章鱼细胞中g(h)的特性,因为它们是在电压钳下用全细胞膜片记录显示的。超极化激活电流I-h被细胞外Cs+(5 mM)和4-(N-乙基-N-苯氨基)-1,2-二甲基-6-(甲氨基)吡啶氯化物(50-100 nM)阻断,但不被细胞外Ba 2+(2 mM)阻断。正常生理条件下章鱼细胞1h的翻转电位为-38mV。将细胞外钾浓度从3 mM增加到12 mM,将逆转电位移至-26 mV;将细胞外钠浓度从138 mM降低到10 mM,将逆转电位移至-77 mV。这些药理学和离子替代实验表明,章鱼细胞中的I-h是一种混合阳离子电流,类似于其他神经元和心肌细胞中的I-h。在对照条件下,当细胞内灌注ATP和GTP时,I-h的激活阈值在约-35至-40 mV之间,并在-110 mV时完全激活。与超极化电压阶跃至-112 mV相关的最大电导范围为87至212 nS [150 +/- 30(SD)nS,n = 36]。从峰值尾电流获得的g(h)的电压依赖性通过半激活电位为-65 +/-3 mV和斜率因子为7.7 +/-0.7的Boltzmann函数拟合。这种关系表明,在章鱼细胞的平均静息电位-62 mV时,g(h)被激活41%,并且在静息时,I-h贡献了0.9至2.1 nA的稳定内向电流。的电压依赖性的g(h)是不受细胞外应用的双丁酰cAMP,但在超极化方向移动,独立的存在或不存在的双丁酰cAMP,通过去除细胞内ATP和GTP。
Octopus cells in the posteroventral cochlear nucleus of mammals detect the coincidence of synchronous firing in populations of auditory nerve fibers and convey the timing of that coincidence with great temporal precision. Earlier recordings in current clamp have shown that two conductances contribute to the low input resistance and therefore to the ability of octopus cells to encode timing precisely, a low-threshold K+ conductance and a hyperpolarization-activated mixed-cation conductance, g(h). The present experiments describe the properties of g(h) in octopus cells as they are revealed under voltage clamp with whole-cell, patch recordings. The hyperpolarization-activated current, I-h, was blocked by extracellular Cs+ (5 mM) and 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyridinium chloride (50-100 nM) but not by extracellular Ba2+ (2 mM). The reversal potential for 1 h in octopus cells under normal physiological conditions was -38 mV. Increasing the extracellular potassium concentration from 3 to 12 mM shifted the reversal potential to -26 mV; lowering extracellular sodium concentration from 138 to 10 mM shifted the reversal potential to -77 mV. These pharmacological and ion substitution experiments show that I-h in octopus cells is a mixed-cation current that resembles I-h in other neurons and in heart muscle cells. Under control conditions when cells were perfused intracellularly with ATP and GTP, I-h had an activation threshold between about -35 to -40 mV and became fully activated at -110 mV. The maximum conductance associated with hyperpolarizing voltage steps to -112 mV ranged from 87 to 212 nS [150 +/- 30 (SD) nS, n = 36]. The voltage dependence of g(h) obtained from peak tail currents is fit by a Boltzmann function with a half-activation potential of -65 +/- 3 mV and a slope factor of 7.7 +/- 0.7. This relationship reveals that g(h) was activated 41% at the mean resting potential of octopus cells, -62 mV, and that at rest I-h contributes a steady inward current of between 0.9 and 2.1 nA. The voltage dependence of g(h) was unaffected by the extracellular application of dibutyryl cAMP but was shifted in hyperpolarizing direction, independent of the presence or absence of dibutyryl cAMP, by the removal of intracellular ATP and GTP.