PT  - JOURNAL ARTICLE
AU  - Lorcan Browne
AU  - Katie E. Smith
AU  - Daniel J. Jagger
TI  - Identification of Persistent and Resurgent Sodium Currents in Spiral Ganglion Neurons Cultured from the Mouse Cochlea
AID  - 10.1523/ENEURO.0303-17.2017
DP  - 2017 Nov 07
TA  - eneuro
PG  - ENEURO.0303-17.2017
4099  - http://www.eneuro.org/content/early/2017/11/07/ENEURO.0303-17.2017.short
4100  - http://www.eneuro.org/content/early/2017/11/07/ENEURO.0303-17.2017.full
AB  - In spiral ganglion neurons (SGNs), the afferent single units of the auditory nerve, high spontaneous and evoked firing rates ensure preservation of the temporal code describing the key features of incoming sound. During postnatal development, the spatiotemporal distribution of ion channel subtypes contributes to the maturation of action potential generation in SGNs, and to their ability to generate spike patterns that follow rapidly changing inputs. Here we describe tetrodotoxin-sensitive Na+ currents in SGNs cultured from mice, whose properties may support this fast spiking behavior. A sub-threshold persistent Na+ current (INaP) and a resurgent Na+ current (INaR) both emerged prior to the onset of hearing and became more prevalent as mouse hearing matured. Navβ4 subunits, which are proposed to play a key role in mediating INaR elsewhere in the nervous system, were immunolocalized to the first heminode where spikes are generated in the auditory nerve, and to peri-somatic nodes of Ranvier. ATX-II, a sea anemone toxin that slows classical Na+ channel inactivation selectively, enhanced INaP five-fold and INaR three-fold in voltage clamp recordings. In rapidly-adapting SGNs under current clamp, ATX-II increased the likelihood of firing additional action potentials. The data identify INaP and INaR as novel regulators of excitability in SGNs, and consistent with their roles in other neuronal types, we suggest that these non-classical Na+ currents may contribute to the control of refractoriness in the auditory nerve.Significance Statement Neurons in the auditory nerve are renowned for their ability to fire action potentials at high rates. This is essential for the brain’s normal coding of acoustic signals, and in humans this information is important for deciphering speech, and for determining the frequency and loudness of sounds. Here, we describe mechanisms that may contribute to this rapid spiking. Non-classical Na+ currents increase the excitability and decrease the refractoriness of spiral ganglion neurons, enabling them to fire spikes at high rates for prolonged periods. Knowing how these currents contribute to normal auditory nerve function may improve our understanding of peripheral auditory neuropathies, and identify novel drug targets for the treatment of conditions causing hearing loss.