Low-threshold, persistent sodium current in rat large dorsal root ganglion neurons in culture

Low-threshold, persistent sodium current in rat large dorsal root ganglion neurons in culture
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DOI:
10.1152/jn.1997.77.3.1503
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发表时间:
1997-03-01
影响因子:
2.5
通讯作者:
Bostock, H
Bostock, H
中科院分区:
医学3区
文献类型:
--
作者:
Baker, MD;Bostock, H

文献摘要

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取成年大鼠背根神经节神经元(大于或等于200g),培养1~3d。用全细胞膜片钳技术记录大神经元(表观直径50~75微米)产生的膜电流。大型神经元产生瞬时Na+电流和至少两种类型的内向电流,这种电流持续了200毫秒的电压钳阶跃至+20 mV。一个持续电流激活接近-35 mV(高阈值),而在大约一半的细胞中,另一个持续电流开始激活负的-70 mV(低阈值)。高阈值持续电流被确认为钙电流,正如先前在这些神经元中所描述的那样。用四甲基铵离子替代外源Na+或降低外源Na+浓度([Na+]),同时升高外源[Ca~(2+)],可可逆地抑制低阈值电流。被河豚毒素(TTX)阻断,其表观平衡解离常数在单纳摩尔范围内,我们认为该低阈值电流是TTX敏感的、持久的Na+电流。持续的TTX敏感电流对稳态膜电流的贡献至少从-70 mV到0 mV,比瞬时Na+电流的激活-失活门控重叠所预测的电位范围更宽。由于其低的阈值和快速的激活动力学,持续的Na+电流有望在决定膜的兴奋性方面发挥重要作用。
Dorsal root ganglion neurons from adult rats (greater than or equal to 200 g) were maintained in culture for between 1 and 3 days. Membrane currents generated by large neurons (50-75 mu m apparent diameter) were recorded with the whole cell patch-clamp technique. Large neurons generated transient Na+ currents and at least two types of inward current that persisted throughout 200-ms voltage-clamp steps to +20 mV. One persistent current activated close to -35 mV (high threshold), whereas in about half of the cells another persistent current began to activate negative to -70 mV (low threshold). The high-threshold persistent current was identified as a Ca2+ current, as previously described in these neurons. The low-threshold current was reversibly suppressed either by replacing external Na+ with tetramethylammonium ions or by reducing external Na+ concentration ([Na+]) and simultaneously raising external [Ca2+]. It was blocked by tetrodotoxin (TTX) with an apparent equilibrium dissociation constant in the single nanomolar range, We conclude that the low-threshold current is a TTX-sensitive, persistent Na+ current. The persistent TTX-sensitive current contributed to steady-state membrane current from at least -70 mV to 0 mV, a wider potential range than predicted by activation-inactivation gating overlap for transient Na+ current. Because of its low threshold and fast activation kinetics, the persistent Na+ current is expected to play an important role in determining membrane excitability.