Tetrodotoxin-, dihydropyridine-, and riluzole-resistant persistent inward current: novel sodium channels in rodent spinal neurons
Tetrodotoxin-, dihydropyridine-, and riluzole-resistant persistent inward current: novel sodium channels in rodent spinal neurons
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DOI：
10.1152/jn.00918.2010
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发表时间：
2011-09-01
影响因子：
2.5
通讯作者：
Jordan, Larry M.
中科院分区：
文献类型：
--
作者：
Dai, Yue;Jordan, Larry M.
戴Y，乔丹LM。河豚毒素、二氢吡啶和利鲁唑耐药的持续内向电流：啮齿动物脊髓神经元中的新型钠通道。 《神经生理学杂志》106：1322-1340，2011 年。首次发表于 2011 年 6 月 8 日； doi:10.1152/jn.00918.2010.-最近，我们报道了新生小鼠脊髓神经元中的河豚毒素 (TTX) 和二氢吡啶 (DHP) 抗性 (TDR) 内向电流。在本研究中，我们进一步表征了存在 1-5 μM TTX 和 20-30 μM DHP（硝苯地平、尼莫地平或伊拉地平）时的电流。 TDR 内向电流通过电压斜坡（持续内向电流，TDR-PIC）和阶跃（TDR-I(p)）协议进行记录。在 80.2% 的记录神经元 (101/126) 中发现了 TDR-PIC 和 TDR-I(p)，该神经元穿过从 T12 到 L6 的 I 层到 X 层。 TDR-PIC 在 -8.6 +/- 13 mV 时激活，幅度为 80.6 +/- 75 pA，时间常数为 470.6 +/- 240 ms (n = 75)。 TDR-I(p) 的振幅为 151.2 +/- 151 pA，电压阈值为 -7.0 +/- 9 mV (n = 54)，具有多种动力学参数。半最大激活为 -21.5 +/- 8 mV（-37 至 -12 mV，n = 29），时间常数为 5.2 +/- 2 ms（1.2-11.2 ms，n = 19），而半最大失活为 -26.9 +/- 9 mV（-39 至 -18 mV，n = 14），时间常数为 1.4 +/- 0.4 秒（0.5-2.2 秒，n = 19）。 TDR-PIC 和 TDR-I(p) 在零钙溶液中可降低 60%，在零钠溶液中可完全去除，表明它们是由钠离子介导的。此外，TDR-I(p) 的反转电位估计为 56.6 +/- 3 mV (n = 10)。 TDR-PIC和TDR-I(p)在1-205μM TTX、20-100μM DHP、3-30μM利鲁唑、50-300μM氟芬那酸和2-30mM细胞内BAPTA中持续存在。他们还坚持使用 T、N、P/Q 和 R 型钙通道阻滞剂。总之，我们在新生啮齿动物脊髓神经元中证明了新的 TTX、DHP 和利鲁唑耐药钠通道。独特的药理学和电生理学特性将使这些通道在脊髓运动系统中发挥功能作用。
Dai Y, Jordan LM. Tetrodotoxin-, dihydropyridine-, and riluzole-resistant persistent inward current: novel sodium channels in rodent spinal neurons. J Neurophysiol 106: 1322-1340, 2011. First published June 8, 2011; doi:10.1152/jn.00918.2010.-Recently, we reported the tetrodotoxin (TTX)- and dihydropyridine (DHP)-resistant (TDR) inward currents in neonatal mouse spinal neurons. In this study, we further characterized these currents in the presence of 1-5 mu M TTX and 20-30 mu M DHP (nifedipine, nimodipine, or isradipine). TDR inward currents were recorded by voltage ramp (persistent inward current, TDR-PIC) and step (TDR-I(p)) protocols. TDR-PIC and TDR-I(p) were found in 80.2% of recorded neurons (101/126) crossing laminae I to X from T12 to L6. TDR-PIC activated at -8.6 +/- 13 mV with an amplitude of 80.6 +/- 75 pA and time constant of 470.6 +/- 240 ms (n = 75). TDR-I(p) had an amplitude of 151.2 +/- 151 pA and a voltage threshold of -7.0 +/- 9 mV (n = 54) with a wide range of kinetics parameters. The half-maximal activation was -21.5 +/- 8 mV (-37 to -12 mV, n = 29) with a time constant of 5.2 +/- 2 ms (1.2-11.2 ms, n = 19), whereas the half-maximal inactivation was -26.9 +/- 9 mV (-39 to -18 mV, n = 14) with a time constant of 1.4 +/- 0.4 s (0.5-2.2 s, n = 19). TDR-PIC and TDR-I(p) could be reduced by 60% in zero calcium and completely removed in zero sodium solutions, suggesting that they were mediated by sodium ions. Furthermore, the reversal potential of TDR-I(p) was estimated as 56.6 +/- 3 mV (n = 10). TDR-PIC and TDR-I(p) persisted in 1-205 mu M TTX, 20-100 mu M DHP, 3-30 mu M riluzole, 50-300 mu M flufenamic acid, and 2-30 mM intracellular BAPTA. They also persisted with T-, N-, P/Q-, and R-type calcium channel blockers. In conclusion, we demonstrated novel TTX-, DHP-, and riluzole-resistant sodium channels in neonatal rodent spinal neurons. The unique pharmacological and electrophysiological properties would allow these channels to play a functional role in spinal motor system.