SLOW SODIUM CONDUCTANCES OF DORSAL-ROOT GANGLION NEURONS - INTRANEURONAL HOMOGENEITY AND INTERNEURONAL HETEROGENEITY
SLOW SODIUM CONDUCTANCES OF DORSAL-ROOT GANGLION NEURONS - INTRANEURONAL HOMOGENEITY AND INTERNEURONAL HETEROGENEITY
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DOI：
10.1152/jn.1994.72.6.2796
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发表时间：
1994-12-01
影响因子：
2.5
通讯作者：
WAXMAN, SG
中科院分区：
文献类型：
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作者：
RIZZO, MA;KOCSIS, JD;WAXMAN, SG
1.用全细胞膜片钳技术研究了成年大鼠背根神经节（DRG）小神经元（直径18-25 μ m）电压依赖性Na ~+电导。Na+电流也记录了较大（44-50 μ m直径）的神经元，并与小神经元的Na+电流进行比较.主要的Na+电导在小神经元的选择性超过四甲基铵至少10倍，并耐1 μ M的外部河豚毒素（TTX）。Na+电导在许多较大的DRG神经元动力学更快，相反，被1 μ M TTX.3。小神经元的Na+电导在动力学上是缓慢的。激活半衰期具有电压依赖性，范围为-20 mV时的2 ms至+50 mV时的0.7 ms。大约50%的激活半衰期由初始延迟组成。失活半衰期是电压依赖性的，范围从-20 mV的11 ms到+50 mV的2 ms。当条件电位负至-120 mV时，峰值慢Na+电导接近最大值，当条件电位正至-40 mV时，峰值慢Na+电导显著降低或消除。在-40 ~+40 mV范围内，随着测试电位的增加，慢Na+电导逐渐增加。在某些细胞中，电导可以在+10 mV时饱和。峰值电导/电压关系，虽然在给定的神经元中稳定，但在神经元之间显示出显著的可变性，分别跨越稳态激活和失活（电流可用性）的>20和50 mV域。在实验过程中，给定神经元内的动力学保持稳定。然而，从神经元到神经元表现出相当大的动力学变化，使得激活和失活的半衰期跨越一个数量级。在所有研究的小神经元中，基于对条件电位的敏感性、激活的电压依赖性和失活半衰期，似乎存在电流的单一动力学分量。小神经元的Na+通道表现出独特的关闭特性。去极化诱导的完全失活状态后的超极化导致尾电流，这似乎是重新激活的慢Na+电导的后果。在固定水平的去极化过程中不同时间记录的尾电流显示，在前一个去极化过程中，潜在的通道积累成挥发性失活状态。较大的神经元有不同的剧目的Na+电导，要么只有一个TTX敏感，动力学快的类型，或快速TTX敏感和慢电流的组合。在较大的神经元中，动力学上可分离的快电流对条件电位具有更大的敏感性，即，左移的稳态失活曲线。不同神经元的慢Na+电导的不同性质可能反映了底层通道分子结构的异质性。虽然与其他人在等效制剂中发现的一致，但这种异质性的范围远比迄今为止所描述的要广。我们认为，在一个给定的小神经元内的生物合成的限制保持离子通道的均匀性。
1. Voltage-dependent Na+ conductances were studied in small (18-25 mu m diam) adult rat dorsal root ganglion (DRG) neurons with the use of the whole cell patch-clamp technique. Na+ currents were also recorded from larger (44-50 mu m diam) neurons and compared with those of the small neurons.2. The predominant Na+ conductance in the small neurons was selective over tetramethylammonium by at least 10-fold and was resistant to 1 mu M external tetrodotoxin (TTX). Na+ conductances in many larger DRG neurons were kinetically faster and, in contrast, were blocked by 1 mu M TTX.3. The Na+ conductance in the small neurons was kinetically slow. Activation half-times were voltage dependent and ranged from 2 ms at -20 mV to 0.7 ms at +50 mV. Approximately 50% of the activation half-time was comprised of an initial delay. Inactivation half-times were voltage dependent and ranged from II ms at -20 mV to 2 ms at +50 mV.4. Peak slow Na+ conductances were near maximal with conditioning potentials negative to -120 mV and were significantly reduced or eliminated with conditioning potentials positive to -40 mV. The slow Na+ conductance increased gradually with test potentials extending from -40 to +40 mV. In some cells the conductance could be saturated at +10 mV. Peak conductance/ voltage relationships, although stable in a given neuron, revealed marked variability among neurons, spanning >20- and 50-mV domains for steady-state activation and inactivation (current availability), respectively.5. Kinetics remained stable within a given neuron over the course of an experiment. However, considerable kinetic variation was exhibited from neuron to neuron, such that the half-times of activation and of inactivation spanned an order of magnitude. In all small neurons studied there appeared to be a singular kinetic component of the current, based on sensitivity to the conditioning potential, voltage dependence of activation, and inactivation halftime.6. Unique closing properties were exhibited by Na+ channels of the small neurons. Hyperpolarization following a depolarization-induced fully inactivated state resulted in tail currents that appeared to be the consequence of reactivation of the slow Na+ conductance. Tail currents recorded at various times during a fixed level of depolarization revealed that the underlying channels accumulated into a volatile inactivated state over the course of the preceding depolarization.7. Larger neurons had a different repertoire of Na+ conductances, with either only a TTX-sensitive, kinetically fast type, or a combination of fast TTX-sensitive and slow currents. In larger neurons the kinetically separable fast current had a greater sensitivity to the conditioning potential, i.e., a left-shifted steady-state inactivation curve.8. The different properties of the slow Na+ conductance in different neurons is likely to reflect heterogeneity of the structure of the underlying channel molecule. Although consistent with what others have found in equivalent preparations, this heterogeneity is far broader in scope than what has so far been described. We suggest that biosynthetic constraints within a given small neuron maintain ion channel uniformity.