2022 MSC Poster Contest Presentation: The Potassium Channel Subunit Kv1.8 (Kcna10) Differentially Shapes Gain, Tuning, and Timing of Receptor Potentials in Type I and II Vestibular Hair cells

Title: The potassium channel subunit Kv1.8 (Kcna10) differentially shapes gain, tuning, and timing of receptor potentials in type I and II vestibular hair cells

Presenter: Hannah Martin, PhD student, University of Chicago, US

Methodology, findings and conclusions of the research
Vestibular hair cells convert head motions into receptor potentials that drive synaptic transmission, enabling rapid gaze- and posture-stabilizing reflexes, spatial navigation, and gravity sensing. Type I and II hair cells are contacted by calyceal and bouton terminals, respectively, and express two different voltage-gated K+ conductances with specialized biophysical properties that differently tune receptor potentials and are thought to impact the nature of synaptic transmission onto calyceal terminals.

We studied the Kv conductances in type I and II hair cells from utricles of mice wildtype, heterozygous, and null for the pore-forming subunit, Kv1.8 (Lee et al. 2013, Hearing Research. 300:1-9). We found that Kv1.8 is necessary for the two different dominant K+ conductances in vestibular hair cells: the low-voltage-activated gK,L in type I hair cells and the inactivating A-type gA in type II hair cells. Kv1.8 is localized on the basolateral membrane of type I and II hair cells, where synapses are located.

In comparison to Kv1.8-null hair cells, Kv1.8 reduces receptor potential gain and latency, an expected outcome based on its effect on input resistance. In both type I and II hair cells, Kv1.8 lowers the lowpass corner frequency of receptor potentials re: mechanical bundle displacement from >70 Hz to ~20 Hz. In both cases, the presence of KV1.8 was necessary to keep lowpass corner frequencies well above the physiological range of head motions (~0-20 Hz, Carriot et al. 2017, J Physio. 595:2751-2766). This may be important for detecting and responding to high frequency head motions.

We tested this prediction by comparing specific vestibulomotor behaviors in Kv1.8-control and Kv1.8-null mice. We found that Kv1.8-null mice have abnormal swim posture, show signs of difficulty in crossing a narrow balance beam, and are less likely to engage in unstable upright or rearing postures. Altogether, these results investigated how a K+ channel subunit in vestibular hair cells plays a role in detecting high frequency head motions and enabling effective vestibulomotor behaviors.

Implications of the research for understanding migraine and/or its comorbidities
Our mouse model relates the physiological impact of a null mutation of Kv1.8 to its impact on vestibulomotor behaviors. This gives us a handle to interrogate basic signaling circuits in early vestibular processing. For example, fluid homeostasis (endolymph ion flow) is currently a very active area of research in disorders of the inner ear; however, we have yet to understand how Kv1.8, a potassium channel that gives type I hair cells an unusually large resting potassium conductance, supports that fluid homeostasis. By understanding the exact role of Kv1.8, we may uncover new therapeutic targets. Lastly, developing better tools to assess vestibular function in awake behaving mice is a growing interest of mine. In general, basic research benefits from methodological improvements. Specifically, our ongoing and collaborative work to develop better tools for investigating vestibulomotor behaviors will contribute to assessing migraine-like symptoms in other mice models as well.