Effect of M-current modulation on mammalian vestibular responses to transient head motion

In this study we used the KCNQ antagonist XE991 and the KCNQ activator retigabine in anesthetized mice to evaluate the effects of M-current modulation on peripheral vestibular responses to transient head motion. At low doses of XE991, responses were modestly enhanced, becoming larger in amplitude and shorter in latency. Higher doses of XE991 produced transient response enhancement, followed by steady-state suppression where latencies and thresholds increased and amplitudes decreased. Retigabine produced opposite effects. Auditory function was also impacted, based on results of companion auditory brain stem response testing. We propose that closure of KCNQ channels transforms vestibular afferent behavior by suppressing responses to transient high-frequency stimuli while simultaneously enhancing responses to sustained low-frequency stimulation. Our results clearly demonstrate that KCNQ channels are critical for normal mammalian vestibular function and suggest that efferent action may utilize these mechanisms to modulate the dynamic characteristics and gain of vestibular afferent responses. NEW & NOTEWORTHY The role of calyceal KCNQ channels and associated M-current in normal mammalian vestibular function is unknown. Our results show that calyceal KCNQ channels are critical for normal vestibular function in the intact mammal. The findings provide evidence that efferent modulation of M-currents may act normally to differentially adjust the sensitivity of vestibular neurons to...
Source: Journal of Neurophysiology - Category: Neurology Authors: Tags: Research Articles Source Type: research