Neuroscience Research Australia, Barker St, Randwick, Sydney, NSW 2031, Australia.
J Physiol. 2013 Jan 1;591(1):273-86. doi: 10.1113/jphysiol.2012.240820. Epub 2012 Sep 24.
While substantial alterations in myelination and axonal growth have been described during maturation, their interactions with the configuration and activity of axonal membrane ion channels to achieve impulse conduction have not been fully elucidated. The present study utilized axonal excitability techniques to compare the changes in nerve function across healthy infants, children, adolescents and adults. Multiple excitability indices (stimulus-response curve, strength-duration time constant, threshold electrotonus, current-threshold relationship and recovery cycle) combined with conventional neurophysiological measures were investigated in 57 subjects (22 males, 35 females; age range 0.46-24 years), stimulating the median motor nerve at the wrist. Maturational changes in conduction velocity were paralleled by significant alterations in multiple excitability parameters, similarly reaching steady values in adolescence. Maturation was accompanied by reductions in threshold (P < 0.005) and rheobase (P = 0.001); depolarizing and hyperpolarizing electrotonus progressively reduced (P < 0.001), or 'fanned-in'; resting current-threshold slope increased (P < 0.0001); accommodation to depolarizing currents prolonged (P < 0.0001); while greater threshold changes in refractoriness (P = 0.001) and subexcitability (P < 0.01) emerged. Taken together, the present findings suggest that passive membrane conductances and the activity of K(+) conductances decrease with formation of the axo-glial junction and myelination. In turn, these functional alterations serve to enhance the efficiency and speed of impulse conduction concurrent with the acquisition of motor skills during childhood, and provide unique insight into the evolution of postnatal human peripheral nerve function. Significantly, these findings bring the dynamics of axonal development to the clinical domain and serve to further illuminate pathophysiological mechanisms that occur during development.
虽然在成熟过程中已经描述了髓鞘形成和轴突生长的实质性改变，但它们与轴突膜离子通道的构象和活性的相互作用，以实现冲动传导，尚未得到充分阐明。本研究利用轴突兴奋性技术比较了健康婴儿、儿童、青少年和成年人的神经功能变化。在 57 名受试者（22 名男性，35 名女性；年龄范围 0.46-24 岁）中，结合常规神经生理学测量，研究了多个兴奋性指数（刺激-反应曲线、强度-持续时间时间常数、阈电紧张、电流-阈关系和恢复周期），刺激腕部正中运动神经。传导速度的成熟变化伴随着多个兴奋性参数的显著改变，同样在青春期达到稳定值。成熟伴随着阈值（P < 0.005）和基强度（P = 0.001）的降低；去极化和超极化电紧张逐渐降低（P < 0.001），或“扇形展开”；静息电流-阈斜率增加（P < 0.0001）；去极化电流适应延长（P < 0.0001）；而在反射性和亚兴奋性（P < 0.01）的阈变化更大。总之，这些发现表明，随着轴突-胶质连接的形成和髓鞘的形成，被动膜电导和 K+电导的活性降低。反过来，这些功能改变有助于提高冲动传导的效率和速度，同时伴随着儿童期运动技能的获得，并为出生后人类周围神经功能的演变提供了独特的见解。重要的是，这些发现将轴突发育的动力学引入临床领域，并有助于进一步阐明发育过程中发生的病理生理机制。
