Zhu J J, Uhlrich D J, Lytton W W
Department of Anatomy, University of Wisconsin Medical School and Wm. S. Middleton VA Hospital, Madison 53706, USA.
Neuroscience. 1999;92(2):445-57. doi: 10.1016/s0306-4522(98)00759-3.
A hyperpolarization-activated cation conductance contributes to the membrane properties of a variety of cell types. In the thalamus, a prominent hyperpolarization-activated cation conductance exists in thalamocortical cells, and this current is implicated in the neuromodulation of complex firing behaviors. In contrast, the GABAergic cells in the reticular nucleus in the thalamus appear to lack this conductance. The presence and role of this cation conductance in the other type of thalamic GABAergic cells, local interneurons, is still unclear. To resolve this issue, we studied 54 physiologically and morphologically identified local interneurons in the rat dorsal lateral geniculate nucleus using an in vitro whole-cell patch recording technique. We found that hyperpolarizing current injections induced depolarizing voltage sags in these geniculate interneurons. The I-V relationship revealed an inward rectification. Voltage-clamp study indicated that a slow, hyperpolarization-activated cation conductance was responsible for the inward rectification. We then confirmed that this slow conductance had properties of the hyperpolarization-activated cation conductance described in other cell types. The slow conductance was insensitive to 10 mM tetraethylammonium and 0.5 mM 4-aminopyridine, but was largely blocked by 1-1.5 mM Cs+. It was permeable to both K+ and Na+ ions and had a reversal potential of -44 mV. The voltage dependence of the hyperpolarization-activated cation conductance in interneurons was also studied: the activation threshold was about -55 mV, half-activation potential was about -80 mV and maximal conductance was about 1 nS. The activation and deactivation time constants of the conductance ranged from 100 to 1000 ms, depending on membrane potential. The depolarizing voltage sags and I-V relationship were further simulated in a model interneuron, using the parameters of the hyperpolarization-activated cation conductance obtained from the voltage-clamp study. The time-course and voltage dependence of the depolarizing voltage sags and I-V relationship in the model cell were very similar to those found in geniculate interneurons in current clamp. Taken together, the results of the present study suggest that thalamic local interneurons possess a prominent hyperpolarization-activated cation conductance, which may play important roles in determining basic membrane properties and in modulating firing patterns.
一种超极化激活的阳离子电导作用于多种细胞类型的膜特性。在丘脑，丘脑皮质细胞中存在显著的超极化激活阳离子电导，并且这种电流与复杂放电行为的神经调节有关。相比之下，丘脑网状核中的γ-氨基丁酸能细胞似乎缺乏这种电导。这种阳离子电导在丘脑另一类γ-氨基丁酸能细胞即局部中间神经元中的存在及作用仍不清楚。为解决这一问题，我们使用体外全细胞膜片钳记录技术研究了大鼠背侧外侧膝状核中54个经生理和形态学鉴定的局部中间神经元。我们发现，向这些膝状中间神经元注入超极化电流会诱发去极化电压凹陷。电流-电压关系显示出内向整流。电压钳研究表明，一种缓慢的、超极化激活的阳离子电导是内向整流的原因。然后我们证实这种缓慢的电导具有其他细胞类型中描述的超极化激活阳离子电导的特性。这种缓慢的电导对10 mM四乙铵和0.5 mM 4-氨基吡啶不敏感，但在很大程度上被1 - 1.5 mM Cs⁺阻断。它对K⁺和Na⁺离子都有通透性，反转电位为 -44 mV。我们还研究了中间神经元中超极化激活阳离子电导的电压依赖性：激活阈值约为 -55 mV，半激活电位约为 -80 mV，最大电导约为1 nS。电导的激活和失活时间常数范围为100至1000 ms，这取决于膜电位。利用从电压钳研究中获得的超极化激活阳离子电导参数，在模型中间神经元中进一步模拟了去极化电压凹陷和电流-电压关系。模型细胞中去极化电压凹陷和电流-电压关系的时间进程和电压依赖性与电流钳记录中膝状中间神经元的情况非常相似。综上所述，本研究结果表明丘脑局部中间神经元具有显著的超极化激活阳离子电导，这可能在决定基本膜特性和调节放电模式中发挥重要作用。
