HYPERPOLARIZATION-ACTIVATED CATION CURRENT (I(H)) IN NEURONS OF THE MEDIAL NUCLEUS OF THE TRAPEZOID BODY - VOLTAGE-CLAMP ANALYSIS AND ENHANCEMENT BY NOREPINEPHRINE AND CAMP SUGGEST A MODULATORY MECHANISM IN THE AUDITORY BRAIN-STEM
HYPERPOLARIZATION-ACTIVATED CATION CURRENT (I(H)) IN NEURONS OF THE MEDIAL NUCLEUS OF THE TRAPEZOID BODY - VOLTAGE-CLAMP ANALYSIS AND ENHANCEMENT BY NOREPINEPHRINE AND CAMP SUGGEST A MODULATORY MECHANISM IN THE AUDITORY BRAIN-STEM
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DOI：
10.1152/jn.1993.70.4.1420
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发表时间：
1993-10-01
影响因子：
2.5
通讯作者：
SMITH, PH
中科院分区：
文献类型：
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作者：
BANKS, MI;PEARCE, RA;SMITH, PH
1. 梯形体内侧核 (MNTB) 中的主细胞是上橄榄复合体 (SOC) 中回路的一部分，该回路处理对声音定位很重要的双耳信息。 MNTB 细胞有两个在接近静止时活跃的电压依赖性电流，这有助于这些细胞的高度非线性膜特性并塑造它们对突触输入的响应。其中一种电流是低阈值、4-氨基吡啶 (4-AP) 敏感的 K+ 电流，之前已在电流钳下进行了研究。使用单电极电压钳技术，我们研究了大鼠 SOC.2 脑切片中的另一种电流，即超极化激活的混合阳离子电流 (I(h))。 I(h) 是 MNTB 细胞电流钳下记录的稳定超极化电流电压响应中显着“下垂”的原因。在电压钳记录中，来自静息电位的超极化电压阶跃引发了大的内向电流，该电流以双指数动力学激活和失活。激活时间常数与电压有关，tau1 和 tau2 在 -75 mV 时分别 = 246 和 1620 ms，在 -100 mV 时分别 = 107 和 560 ms。3。 I(h) 被 1-5 mM 铯阻断，反转电位为 -43 mV。由尾电流导出的稳态激活曲线产生 -75.7 mV 的半激活电压和 5.7 mV 的斜率因子，对应于静止状态下 I(h) 的 < 10% 激活率。4。去甲肾上腺素 (15-20 muM) 或 8-溴腺苷 3',5'-环单磷酸 (8-Br-cAMP) (1 mM) 的应用引起稳态激活曲线的去极化偏移并降低激活时间常数。激活曲线的移动导致静息时 I(h) 的激活大幅增加、保持电流向内移动以及静息膜电导增加。在电流钳记录中，I(h) 静息激活水平的增加导致在不存在 4-AP 的情况下膜去极化 2-3 mV，在存在 4-AP 的情况下导致膜去极化 5-10 mV，输入电导增加，并且响应超极化电流的电压骤降减少。 5。暴露于去甲肾上腺素或 8-Br-cAMP 的 MNTB 细胞的静息点发生变化，可能会改变这些细胞对突触输入的反应，既通过对静息膜电导的直接影响，又通过改变低阈值、4-AP 敏感钾电流的激活。因此，去甲肾上腺素能输入以及与 8-Br-cAMP 产生相关的其他输入激活 I(h) 是调节 MNTB 细胞声信号处理能力的潜在机制。
1. Principal cells in the medial nucleus of the trapezoid body (MNTB) are part of a circuit in the superior olivary complex (SOC) that processes binaural information important for sound localization. MNTB cells have two voltage-dependent currents active near rest that contribute to these cells' highly nonlinear membrane properties and shape their responses to synaptic input. One of these currents, a low-threshold, 4-aminopyridine (4-AP)-sensitive K+ current, has been studied previously under current clamp. Using the single-electrode voltage-clamp technique, we have investigated the other of these currents, a hyperpolarization-activated, mixed cation current (I(h)), in brain slices of the rat SOC.2. I(h) is responsible for a prominent ''sag'' in the voltage response to a steady hyperpolarizing current recorded under current clamp in MNTB cells. In voltage-clamp recordings, hyperpolarizing voltage steps from the resting potential elicited a large inward current that activated and deactivated with biexponential kinetics. Activation time constants were voltage dependent, with tau1 and tau2 = 246 and 1620 ms at -75 mV and 107 and 560 ms at -100 mV.3. I(h) was blocked by 1-5 mM cesium and had a reversal potential of -43 mV. Steady-state activation curves derived from tail currents yielded a half-activation voltage of -75.7 mV and slope factor of 5.7 mV, corresponding to < 10% activation of I(h) at rest.4. Application of norepinephrine (15-20 muM) or 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) (1 mM) caused a depolarizing shift in the steady-state activation curve and decreased the activation time constants. The shift in the activation curve resulted in a large increase in the activation of I(h) at rest, an inward shift in the holding current, and an increase in the resting membrane conductance. In current-clamp recordings, this increase in the resting activation level of I(h) resulted in membrane depolarization of 2-3 mV in the absence of 4-AP, and 5-10 mV in the presence of 4-AP, an increase in the input conductance, and a reduction in the voltage sag in response to hyperpolarizing currents.5. The resulting change in the resting point of MNTB cells exposed to norepinephrine or 8-Br-cAMP is likely to alter the responses of these cells to synaptic input, both via the direct effect on the resting membrane conductance and by changing the activation of the low-threshold, 4-AP-sensitive potassium current. Thus, activation of I(h) by noradrenergic inputs, as well as other inputs linked to 8-Br-cAMP production, is a potential mechanism for modulating the acoustic signal processing capabilities of MNTB cells.