De Col Roberto, Messlinger Karl, Carr Richard W
Institute for Physiology and Pathophysiology, University of Erlangen-Nuremberg, Erlangen, Germany.
J Physiol. 2008 Feb 15;586(4):1089-103. doi: 10.1113/jphysiol.2007.145383. Epub 2007 Dec 20.
Axonal conduction velocity varies according to the level of preceding impulse activity. In unmyelinated axons this typically results in a slowing of conduction velocity and a parallel increase in threshold. It is currently held that Na(+)-K(+)-ATPase-dependent axonal hyperpolarization is responsible for this slowing but this has long been equivocal. We therefore examined conduction velocity changes during repetitive activation of single unmyelinated axons innervating the rat cranial meninges. In direct contradiction to the currently accepted postulate, Na(+)-K(+)-ATPase blockade actually enhanced activity-induced conduction velocity slowing, while the degree of velocity slowing was curtailed in the presence of lidocaine (10-300 microm) and carbamazepine (30-500 microm) but not tetrodotoxin (TTX, 10-80 nm). This suggests that a change in the number of available sodium channels is the most prominent factor responsible for activity-induced changes in conduction velocity in unmyelinated axons. At moderate stimulus frequencies, axonal conduction velocity is determined by an interaction between residual sodium channel inactivation following each impulse and the retrieval of channels from inactivation by a concomitant Na(+)-K(+)-ATPase-mediated hyperpolarization. Since the process is primarily dependent upon sodium channel availability, tracking conduction velocity provides a means of accessing relative changes in the excitability of nociceptive neurons.
轴突传导速度根据先前冲动活动的水平而变化。在无髓鞘轴突中，这通常会导致传导速度减慢以及阈值平行升高。目前认为，依赖钠钾ATP酶的轴突超极化是导致这种减慢的原因，但长期以来这一直存在争议。因此，我们研究了支配大鼠脑脊膜的单个无髓鞘轴突重复激活过程中的传导速度变化。与目前被接受的假设直接相反，钠钾ATP酶阻断实际上增强了活动诱导的传导速度减慢，而在利多卡因（10 - 300微摩尔）和卡马西平（30 - 500微摩尔）存在的情况下，速度减慢的程度受到抑制，但在河豚毒素（TTX，10 - 80纳米）存在时则不然。这表明，可用钠通道数量的变化是导致无髓鞘轴突中活动诱导的传导速度变化的最主要因素。在中等刺激频率下，轴突传导速度由每次冲动后残留的钠通道失活与通过伴随的钠钾ATP酶介导的超极化使通道从失活状态恢复之间的相互作用决定。由于该过程主要取决于钠通道的可用性，追踪传导速度提供了一种了解伤害性神经元兴奋性相对变化的方法。
