Role of Kv1.3 Potassium Channels in Auditory Function

Abstract

Kv1.3 is a low threshold voltage-dependent potassium channel involved in various physiological functions. Within the central nervous system, deletion of Kv1.3 gene from mitral cells of the olfactory bulb dramatically increased the sensitivity of the olfactory system. We have recently shown that Kv1.3 channels are present in presynaptic terminals of the medial nucleus trapezoid body (MNTB) within the auditory brainstem and in bouton-like structures on inner and outer hair cells within the cochlea. Whether Kv1.3 channels contribute to auditory function is, however, unknown. We have therefore used in vivo and in vitro approaches to examine the role of Kv1.3 channels in the peripheral and central auditory system. Auditory brainstem responses (ABR) show that the thresholds of ABR are elevated in 2-4 months old Kv1.3-/- KO mice over those in wild type (WT) mice. Latencies of peaks I, II and IV are prolonged in 4 month old Kv1.3 -/- KO mice. In addition, we have found a desynchronization of ABR waves in Kv1.3-/- KO mice suggesting an alteration of synaptic transmission and changes in spike fidelity within auditory pathways. To further investigate the mechanisms of these alterations in ABR waves in Kv1.3-/- KO mice, we carried out in vitro slice recordings of the high fidelity calyx of Held/MNTB synapse. Our preliminary results from whole cell patch-clamp recordings in young mice (P13-17) show that lack of Kv1.3 channels increases the spike frequency and the spike threshold at presynaptic terminals (Calyx of Held) in response to square pulses of injected currents. Our preliminary data showing that loss of Kv1.3 channels primarily influences the properties of presynaptic terminals and of the ABR waves strongly suggest that Kv1.3 channels are required for normal auditory function.