Heterogeneous Potassium Conductances Contribute to the Diverse Firing Properties of Postnatal Mouse Vestibular Ganglion Neurons

Abstract

How mechanical information is encoded in the vestibular periphery has not been clarified. To begin to address the issue we examined the intrinsic firing properties of postnatal mouse vestibular ganglion neurons using the whole cell, tight-seal technique in current-clamp mode. We categorized two populations of neurons based on the threshold required to evoke an action potential. Low-threshold neurons fired with an average minimum current injection of -43 pA, whereas high-threshold neurons required -176 pA. Using sine-wave stimuli, we found that the neurons were inherently tuned with best frequencies that ranged up to 40 Hz. To investigate the membrane properties that contributed to the variability in firing properties we examined the same neurons in voltage-clamp mode. High-threshold neurons had larger cell bodies and whole cell capacitances but a resting conductance density of 0.18 nS/pF, nearly identical to that of low-threshold neurons, suggesting that cell size was an important parameter determining threshold. We also found that vestibular ganglion neurons expressed a heterogeneous population of potassium conductances. TEA-sensitive conductances contributed to the position of the tuning curve in the frequency domain. A 4-AP-sensitive conductance was active at rest and hyperpolarized resting potential, limited spontaneous activity, raised threshold, and prevented repetitive firing. In response to sine-wave stimulation 4-AP-sensitive conductances prevented action potential generation at low frequencies and thus contributed to the high-pass corner of the tuning curve. The mean low-pass corner (about 29 Hz) was determined by the membrane time constant. Together these factors contributed to the sharply tuned, band-pass characteristics intrinsic to postnatal vestibular ganglion neurons.

Ion channels in mammalian vestibular afferents may set regularity of firing

“…They do spike in response to depolarizing currents (Limón et al, 2005;Risner and Holt, 2006), as we illustrate for isolated mouse vestibular ganglion neurons in Fig. 3.…”

“…(Sometimes a single spike is followed by large voltage oscillations, or ringing; this may be a third category or an immature form of the sustained response.) The sustained and transient categories appear to correspond to the 'lowthreshold' and 'high-threshold' categories, respectively, of Risner and Holt (Risner and Holt, 2006), who defined threshold as the Depolarizing steps (bottom panel) evoked large brief Na + currents followed by large steady outward K + currents. The sustained neuron (D) had prominent A and h currents, but it is not established that these differences influence the spike pattern.…”

“…One current was a rapidly inactivating A current, blocked by 4-aminopyridine (4-AP) and dendrotoxin. An A current was also identified in a semi-intact preparation of the mouse vestibular ganglion (Risner and Holt, 2006).…”

“…Dissociated vestibular somata have been studied with the whole-cell patch method by Desmadryl, Chabbert and colleagues (Autret et al, 2005;Chabbert et al, 1997;Chabbert et al, 2001a;Chabbert et al, 2001b;Desmadryl et al, 1997) and by Soto, Vega and colleagues (Limón et al, 2005;Mercado, 2006). Whole-cell patch recordings have also been made from neurons cultured in semi-intact ganglia (Risner and Holt, 2006). Our goal in reviewing the ion channel properties elucidated by these experiments on isolated somata is to consider insights they might provide into the firing regularity of afferent neurons as described with in vivo recordings.…”

“…The sustained neuron (D) had prominent A and h currents, but it is not established that these differences influence the spike pattern. Current thresholds for evoking spikes are frequency-dependent (Risner and Holt, 2006). Differential expression of A and HCN channels may occur, but is unknown.…”