Effects of transient, persistent, and resurgent sodium currents on excitability and spike regularity in vestibular ganglion neurons.

Vestibular afferent neurons occur as two populations, regular and irregular, that provide distinct information about head motions. Differences in spike timing regularity are correlated with the different sensory responses important for vestibular processing. Relative to irregular afferents, regular afferents have more sustained firing patterns in response to depolarizing current steps, are more excitable, and have different complements of ion channels. Models of vestibular regularity and excitability emphasize the influence of increased expression of low-voltage-activated potassium currents in irregular neurons. We investigated the potential impact of different modes of voltage-gated sodium (Na V ) current (transient, persistent, and resurgent) in cell bodies from vestibular ganglion neurons (VGNs), dissociated and cultured overnight. We hypothesized that regular VGNs would show the greatest impact of persistent (non-inactivating) Na V currents and of resurgent Na V currents, which flow when Na V channels are blocked and then unblocked. Whole-cell patch clamp experiments showed that much of the Na V current modes is carried by Na V 1.6 channels. With simulations, we detected little substantial effect in any model VGN of persistent or resurgent modes on regularity of spike timing driven by postsynaptic current trains. For simulated irregular neurons, we also saw little effect on spike rate or firing pattern. For simulated regular VGNs, adding resurgent current changed the detailed timing of spikes during a current step, while the small persistent conductance (less than10% of transient Na V conductance density) strongly depolarized resting potential, altered spike waveform, and increased spike rate. These results suggest that persistent and resurgent Na V current can have a greater effect on the regular VGNs than on irregular VGNs, where low-voltage-activated K conductances dominate.