Molecular and functional differences in voltage-activated sodium currents between GABA projection neurons and dopamine neurons in the substantia nigra
Molecular and functional differences in voltage-activated sodium currents between GABA projection neurons and dopamine neurons in the substantia nigra
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DOI：
10.1152/jn.00305.2011
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发表时间：
2011-12-01
影响因子：
2.5
通讯作者：
Zhou, Fu-Ming
中科院分区：
文献类型：
--
作者：
Ding, Shengyuan;Wei, Wei;Zhou, Fu-Ming
丁S，魏伟，周福民.黑质GABA投射神经元和多巴胺神经元电压激活钠电流的分子和功能差异。J Neurophysiol 106：3019-3034，2011.首次发表于2011年8月31日; doi：10.1152/jn.00305.2011.-黑质网状部（SNr）的GABA投射神经元（GABA神经元）和黑质网状部（SNc）的多巴胺投射神经元（DA神经元）具有显著不同的放电特性。SNc DA神经元发射低频率、长持续时间的尖峰，而SNr GABA神经元发射高频率、短持续时间的尖峰。由于电压激活的钠（Na（V））通道是尖峰产生的关键，不同的放电特性提高的可能性，与DA神经元相比，在SNr GABA神经元中的Na（V）通道具有更高的密度，更快的动力学，和更少的累积失活。定量RT-PCR分析表明，与SNc DA神经元相比，SNr GABA神经元中Na（V）1.1和Na（V）1.6亚基以及Na（V）β 1和Na（V）β 4亚基的mRNA含量更高。这些α亚基和β亚基是形成Na（V）通道的关键亚基，所述Na（V）通道传导瞬时Na V电流（I（NaT））、持续Na电流（I（NaP））和复苏Na电流（I（NaR））。有核膜片钳记录表明，I（NaT）在SNr GABA神经元中比在SNc DA神经元中具有更高的密度、更陡的电压依赖性激活和更快的失活。I（NaT）也恢复得更快，从失活，并有较少的累积失活在SNr GABA神经元比在SNc DA神经元。此外，与黑质DA神经元相比，SNr GABA神经元具有更大的I（NaR）和I（NaP）。阻断I（NaP）诱导SNr GABA神经元比SNc DA神经元更大的超极化。两者合计，这些结果表明，Na V通道中表达的快速尖峰SNr GABA神经元和慢速尖峰SNc DA神经元的定制，以支持其不同的尖峰能力。
Ding S, Wei W, Zhou FM. Molecular and functional differences in voltage-activated sodium currents between GABA projection neurons and dopamine neurons in the substantia nigra. J Neurophysiol 106: 3019-3034, 2011. First published August 31, 2011; doi: 10.1152/jn.00305.2011.-GABA projection neurons (GABA neurons) in the substantia nigra pars reticulata (SNr) and dopamine projection neurons (DA neurons) in substantia nigra pars compacta (SNc) have strikingly different firing properties. SNc DA neurons fire low-frequency, long-duration spikes, whereas SNr GABA neurons fire high-frequency, short-duration spikes. Since voltage-activated sodium (Na(V)) channels are critical to spike generation, the different firing properties raise the possibility that, compared with DA neurons, Na(V) channels in SNr GABA neurons have higher density, faster kinetics, and less cumulative inactivation. Our quantitative RT-PCR analysis on immunohistochemically identified nigral neurons indicated that mRNAs for poreforming Na(V)1.1 and Na(V)1.6 subunits and regulatory Na(V)beta 1 and Na(v)beta 4 subunits are more abundant in SNr GABA neurons than SNc DA neurons. These alpha-subunits and beta-subunits are key subunits for forming Na(V) channels conducting the transient NaV current (I(NaT)), persistent Na current (I(NaP)), and resurgent Na current (I(NaR)). Nucleated patch-clamp recordings showed that I(NaT) had a higher density, a steeper voltage-dependent activation, and a faster deactivation in SNr GABA neurons than in SNc DA neurons. I(NaT) also recovered more quickly from inactivation and had less cumulative inactivation in SNr GABA neurons than in SNc DA neurons. Furthermore, compared with nigral DA neurons, SNr GABA neurons had a larger I(NaR) and I(NaP). Blockade of I(NaP) induced a larger hyperpolarization in SNr GABA neurons than in SNc DA neurons. Taken together, these results indicate that Na V channels expressed in fast-spiking SNr GABA neurons and slow-spiking SNc DA neurons are tailored to support their different spiking capabilities.