Nav 1.5 underlies the 'third TTX-R sodium current' in rat small DRG neurons
Nav 1.5 underlies the 'third TTX-R sodium current' in rat small DRG neurons
复制标题
DOI：
10.1016/s0169-328x(02)00411-4
复制
发表时间：
2002-10-15
期刊：
影响因子：
--
通讯作者：
Waxman, SG
中科院分区：
文献类型：
--
作者：
Renganathan, M;Dib-Hajj, S;Waxman, SG
除Na（v）1.8和Na（v）1.9 Na+通道分别产生慢失活和持续性TTX-R Na+电流外，在E15大鼠背根神经节（DRG）小神经元中，80%可记录到第三种TTX-R Na+电流，其激活和失活均较快，而在成年DRG小神经元中仅为3%。第三TTX-R Na+电流的激活半衰期、失活时间常数、激活和失活中点与Na（v）1.8和Na（v）1.9 Na+电流有显著差异。第三个TTX-R Na+电流的TTX Ki（2.11+/-0.34 μ M）明显低于Na（v）1.8和Nav1.9 Na+电流。第三TTX-R Na+电流对Cd ~（2+）的敏感性更接近心脏Na+电流。需要1 mM Cd 2+的浓度才能完全阻断该电流，这显著低于阻断Na（v）1.8和Na（v）1.9电流所需的5 mM浓度。在E18大鼠DRG神经元中，第三TTX-R Na+通道与Na（v）1.8和Na（v）1.9 Na+通道不共表达，此时所有三种电流均显示出相当的密度。第三TTX-R Na+电流的生理和药理学特征与心脏Na+通道Na（v）1.5的生理和药理学特征相似，RT-PCR和限制性内切酶多态性分析显示，Na（v）1.5在DRG发育过程中的表达模式是平行的。总之，这些结果表明Na（v）1.5在DRG神经元中以发育调节的方式表达，并表明Na（v）1.5 Na+通道产生第三TTX-R电流。(C)2002 Elsevier Science B. V.保留所有权利。
In addition to slow-inactivating and persistent TTX-R Na+ currents produced by Na(v)1.8 and Na(v)1.9 Na+ channels, respectively, a third TTX-R Na+ current with fast activation and inactivation can be recorded in 80% of small neurons of dorsal root ganglia (DRG) from E15 rats, but in only 3% of adult small DRG neurons. The half-time for activation, the time constant for inactivation, and the midpoints of activation and inactivation of the third TTX-R Na+ currents are significantly different from those of Na(v)1.8 and Na(v)1.9 Na+ currents. The estimated TTX K-i (2.11+/-0.34 muM) of the third TTX-R Na+ current is significantly lower than those of Na(v)1.8 and Nav1.9 Na+ currents. The Cd2+ sensitivity of third TTX-R Na+ current is closer to cardiac Na+ currents. A concentration of 1 mM Cd2+ is required to completely block this current, which is significantly lower than the 5 mM required to block Na(v)1.8 and Na(v)1.9 currents. The third TTX-R Na+ channel is not co-expressed with Na(v)1.8 and Na(v)1.9 Na+ channels in DRG neurons of E18 rats, at a time when all three currents show comparable densities. The physiological and pharmacological profiles of the third TTX-R Na+ current are similar to those of the cardiac Na+ channel Na(v)1.5 and RT-PCR and restriction enzyme polymorphism analysis, show a parallel pattern of expression of Na(v)1.5 in DRG during development. Taken together, these results demonstrate that Na(v)1.5 is expressed in a developmentally regulated manner in DRG neurons and suggest that Na(v)1.5 Na+ channel produces the third TTX-R current. (C) 2002 Elsevier Science B.V. All rights reserved.