Sodium channel diversity in the vestibular ganglion : evidence for Nav̳1.5-like and Nav̳1.8-like currents

Abstract

Voltage-gated sodium (Nav) channels are diverse, comprising nine known mammalian subunits, which are classified pharmacologically into tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-insensitive (TTX-1) categories. The pattern of Nav channel expression shapes response properties of neurons, while changes in these expression patterns are related to many pathological conditions. Previous RT-PCR results indicated the expression of a variety of Nav channel subunits in the vestibular ganglion, the sensory ganglion that conveys information about motion and orientation. The expressed subunits included several TTX-1 subunits with unique biophysical properties that have been extensively characterized in somatosensory neurons and the heart, but never reported in published electrophysiological studies of the vestibular ganglion. Using whole-cell patch clamp, we show the presence of two types of TTX-l Nav currents in acutely dissociated rat vestibular ganglion neurons (VGNs) from the first postnatal week: a fast and negatively-inactivating current (midpoint of inactivation: ~-100 mV) that resembled current previously described for the Nav1.5 subunit, and a slower current with a depolarized voltage range of inactivation (midpoint ~-30 mV) which had properties consistent with Nav1.8 channels. All neurons also expressed TTX-S Nav currents with similar properties to those previously described in VGN (midpoint of inactivation: ~-75 mV). The Nav1.5-like current contributed about 10% of the total Nav current, was expressed in most VGNs on the first postnatal day (P1), and gradually decreased in prevalence throughout the first week. The Nav1.8-like current was present in ~25% of cells and was correlated with broader action potentials, higher voltage thresholds, and minimal spike height accommodation. We confirmed the expression of Nav1.8 using a reporter mouse in which fluorescence is restricted to Nav1.8- expressing cells; intense fluorescent signal was seen in many VGN cell bodies and peripheral processes. These results suggest that Nav1.8 may be expressed in non-somatosensory peripheral neurons. Nav channel expression in immature VGNs may contribute to development, while differential expression in adulthood may underlie diversity of mature response properties.