Biophysical Properties of Somatic and Axonal Voltage-Gated Sodium Channels in Midbrain Dopaminergic Neurons

Abstract

Spiking activities of midbrain dopaminergic neurons are critical for key brain functions including motor control and affective behaviors. Voltage-gated Na+ channels determine neuronal excitability and action potential (AP) generation. Previous studies on dopaminergic neuron excitability mainly focused on Na+ channels at the somatodendritic compartments. Properties of axonal Na+ channels, however, remain largely unknown. Using patch-clamp recording from somatic nucleated patches and isolated axonal blebs from the axon initial segment (AIS) of dopaminergic neurons in mouse midbrain slices, we found that AIS channel density is approximately 4–9 fold higher than that at the soma. Similar voltage dependence of channel activation and inactivation was observed between somatic and axonal channels in both SNc and VTA cells, except that SNc somatic channels inactivate at more hyperpolarized membrane potentials (Vm). In both SNc and VTA, axonal channels take longer time to inactivate at a subthreshold depolarization Vm level, but are faster to recover from inactivation than somatic channels. Moreover, we found that immunosignals of Nav1.2 accumulate at the AIS of dopaminergic neurons. In contrast, Nav1.1 and Nav1.6 immunosignals are not detectible. Together, our results reveal a high density of Na+ channels at the AIS and their molecular identity. In general, somatic and axonal channels of both SNc and VTA dopaminergic neurons share similar biophysical properties. The relatively delayed inactivation onset and faster recovery from inactivation of axonal Na+ channels may ensure AP initiation at high frequencies and faithful signal conduction along the axon.