Persistent and resurgent Na⁺ currents in vestibular calyx afferents

Vestibular afferent neurons convey information from hair cells in the peripheral vestibular end organs to central nuclei. Primary vestibular afferent neurons can fire action potentials at high rates and afferent firing patterns vary with the position of nerve terminal endings in vestibular neuroepithelia. Terminals contact hair cells as small bouton or large calyx endings. To investigate the role of Na⁺ currents (I_Na) in firing mechanisms, we investigated biophysical properties of I_Na in calyx-bearing afferents. Whole cell patch-clamp recordings were made from calyx terminals in thin slices of gerbil crista at different postnatal ages: immature [postnatal day (P)5-P8, young (P13-P15), and mature (P30-P45)]. A large transient Na⁺ current (I_NaT) was completely blocked by 300 nM tetrodotoxin (TTX) in mature calyces. In addition, I_NaT was accompanied by much smaller persistent Na⁺ currents (I_NaP) and distinctive resurgent Na⁺ currents (I_NaR), which were also blocked by TTX. ATX-II, a toxin that slows Na⁺ channel inactivation, enhanced I_NaP in immature and mature calyces. 4,9-Anhydro-TTX (4,9-ah-TTX), which selectively blocks Nav1.6 channels, abolished the enhanced I_Na in mature, but not immature, calyces. Therefore, Nav1.6 channels mediate a component of I_NaT and I_NaP in mature calyces, but are minimally expressed at early postnatal days. I_NaR was expressed in less than one-third of calyces at P6-P8, but expression increased with development, and in mature cristae I_NaR was frequently found in peripheral calyces. I_NaR served to increase the availability of Na⁺ channels following brief membrane depolarizations. In current clamp, the rate and regularity of action potential firing decreased in mature peripheral calyces following 4,9-ah-TTX application. Therefore, Nav1.6 channels are upregulated during development, contribute to I_NaT, I_NaP, and I_NaR, and may regulate excitability by enabling higher mean discharge rates in a subpopulation of mature calyx afferents.NEW & NOTEWORTHY Action potential firing patterns differ between groups of afferent neurons innervating vestibular epithelia. We investigated the biophysical properties of Na⁺ currents in specialized vestibular calyx afferent terminals during postnatal development. Mature calyces express Na⁺ currents with transient, persistent, and resurgent components. Nav1.6 channels contribute to resurgent Na⁺ currents and may enhance firing in peripheral calyx afferents. Understanding Na⁺ channels that contribute to vestibular nerve responses has implications for developing new treatments for vestibular dysfunction.