Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Department of Medicine, Washington University School of Medicine, Box 8086, 660 South Euclid Avenue, St. Louis, MO, 63110, USA.
Cell Mol Life Sci. 2018 Oct;75(19):3495-3505. doi: 10.1007/s00018-018-2868-y. Epub 2018 Jul 7.
Purkinje neurons, the sole output of the cerebellar cortex, deliver GABA-mediated inhibition to the deep cerebellar nuclei. To subserve this critical function, Purkinje neurons fire repetitively, and at high frequencies, features that have been linked to the unique properties of the voltage-gated sodium (Nav) channels expressed. In addition to the rapidly activating and inactivating, or transient, component of the Nav current (I) present in many types of central and peripheral neurons, Purkinje neurons, also expresses persistent (I) and resurgent (I) Nav currents. Considerable progress has been made in detailing the biophysical properties and identifying the molecular determinants of these discrete Nav current components, as well as defining their roles in the regulation of Purkinje neuron excitability. Here, we review this important work and highlight the remaining questions about the molecular mechanisms controlling the expression and the functioning of Nav currents in Purkinje neurons. We also discuss the impact of the dynamic regulation of Nav currents on the functioning of individual Purkinje neurons and cerebellar circuits.
浦肯野神经元是小脑皮层的唯一输出神经元，它们将 GABA 能抑制传递到小脑深部核团。为了发挥这一关键功能，浦肯野神经元反复、高频地放电，这与表达的电压门控钠（Nav）通道的独特特性有关。除了存在于许多类型的中枢和周围神经元中的 Nav 电流（I）的快速激活和失活或瞬时成分外，浦肯野神经元还表达持续（I）和复发性（I）Nav 电流。在详细描述这些离散 Nav 电流成分的生物物理特性和确定其分子决定因素，以及确定它们在调节浦肯野神经元兴奋性中的作用方面已经取得了相当大的进展。在这里，我们回顾了这项重要的工作，并强调了关于控制浦肯野神经元中 Nav 电流表达和功能的分子机制的剩余问题。我们还讨论了 Nav 电流的动态调节对单个浦肯野神经元和小脑回路功能的影响。
