Roles of Tetrodotoxin (TTX)-Sensitive Na+ Current, TTX-Resistant Na+ Current, and Ca2+ Current in the Action Potentials of Nociceptive Sensory Neurons
Roles of Tetrodotoxin (TTX)-Sensitive Na+ Current, TTX-Resistant Na+ Current, and Ca2+ Current in the Action Potentials of Nociceptive Sensory Neurons
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DOI：
10.1523/jneurosci.22-23-10277.2002
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发表时间：
2002-12
期刊：
影响因子：
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通讯作者：
Nathaniel T. Blair;B. Bean
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文献类型：
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作者：
Nathaniel T. Blair;B. Bean
伤害性感觉神经元在表达抗河豚毒素（TTX）钠通道携带的电压门控内向电流以及传统TTX敏感钠通道和电压依赖性钙通道携带的电流方面是不寻常的。为了研究这些细胞所携带的电流如何帮助形成小直径背根神经节细胞体的动作电位，我们使用从每个细胞记录的动作电位作为指令电压来给固定的细胞施加电压。使用生理离子组成的细胞内溶液，我们使用通道阻滞剂（TTX用于TTX敏感的钠电流，钙通道阻滞剂的混合物用于钙电流）和离子替代（通过在TTX存在下用n -甲基-d-氨基葡萄糖替代细胞外钠来测量TTX抗电流，并对改变的驱动力进行校正），分离出动作电位期间流动的电流的单个组分。在伤害感受器动作电位上升期间（~ 58%），ttx抗性钠通道迅速激活，携带最大的内向电荷，ttx敏感钠通道也有显著贡献（~ 40%），特别是在阈值附近，而高压激活的钙电流则少得多（~ 2%）。动作电位在下降阶段有一个突出的肩部，这是伤害性神经元的特征。抗ttx钠离子通道在动作电位期间并没有完全失活，并且携带了大部分（58%）在肩部内流动的电流，高压激活的钙离子电流也有显著贡献（39%）。与钙电流不同，耐ttx钠电流不伴有相反的钙活化钾电流，可能提供了一种有效的机制，通过这种机制可以调节动作电位的持续时间（从而调节钙的进入）。
Nociceptive sensory neurons are unusual in expressing voltage-gated inward currents carried by sodium channels resistant to block by tetrodotoxin (TTX) as well as currents carried by conventional TTX-sensitive sodium channels and voltage-dependent calcium channels. To examine how currents carried by each of these helps to shape the action potential in small-diameter dorsal root ganglion cell bodies, we voltage clamped cells by using the action potential recorded from each cell as the command voltage. Using intracellular solutions of physiological ionic composition, we isolated individual components of current flowing during the action potential with the use of channel blockers (TTX for TTX-sensitive sodium currents and a mixture of calcium channel blockers for calcium currents) and ionic substitution (TTX-resistant current measured by the replacement of extracellular sodium by N-methyl-d-glucamine in the presence of TTX, with correction for altered driving force). TTX-resistant sodium channels activated quickly enough to carry the largest inward charge during the upstroke of the nociceptor action potential (∼58%), with TTX-sensitive sodium channels also contributing significantly (∼40%), especially near threshold, and high voltage-activated calcium currents much less (∼2%). Action potentials had a prominent shoulder during the falling phase, characteristic of nociceptive neurons. TTX-resistant sodium channels did not inactivate completely during the action potential and carried the majority (58%) of inward current flowing during the shoulder, with high voltage-activated calcium current also contributing significantly (39%). Unlike calcium current, TTX-resistant sodium current is not accompanied by opposing calcium-activated potassium current and may provide an effective mechanism by which the duration of action potentials (and consequently calcium entry) can be regulated.