The contribution of KCNT2, KCNT1 and SLO1 β3 to physiological and pathophysiological hearing

Schubert, N. (Nick) (2016) The contribution of KCNT2, KCNT1 and SLO1 β3 to physiological and pathophysiological hearing. thesis, Medicine.

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Abstract

English Hearing impairment is a highly prevalent condition, for which we still do not know the exact physiology and pathophysiology, it also has a large impact on the quality of life. Research suggests that ion channels could play an essential role in hearing physiology and pathophysiology. If these channels contribute to these mechanisms, these channels could potentially become drug targets for hearing impairment. This investigation will focus on KCNT2, KCNT1 and Slo1 β3 subunit, which are all part of the Slo family of potassium channels. The role of these proteins is not yet established in the peripheral auditory system. For this investigation KCNT2/KCNT1 double knock-out mice, KCNMB3 knock-out mice and C57/Black6J mice were used as a model. Before the experiment, the mice were genotyped. Hereafter hearing was assessed with auditory brainstem responses at 8kHz, 16kHz and 32kHz at intensities ranging from 20 to 90 dB SPL. After the hearing assessment the mice were sacrificed to extract the cochlear epithelium for immunostaining for KCNT2, KCNT1 and Slo1 β3 to localize these proteins. Results of the experiments suggest that KCNT2 and KCNT1 have an influence in peak I amplitudes of the auditory brainstem responses. However, there is no effect on the absolute hearing thresholds and latencies. Immunostaining did not result in localization of KCNT2 and KCNT1 in the cochlear epithelium. Slo1 β3 is not present in the cochlear epithelium based on the immunostaining. Furthermore, there is no significant difference between the auditory brainstem responses compared to controls. Future experiments should focus more on optimization of procedures of immunostainings and ABRs. Furthermore, susceptibility for NIHL and electrophysiological properties of these proteins in the auditory periphery could also be investigated. Finally, investigating expression of these and other α, β and ! subunits of the Slo family of potassium channels could lead to new insights in hearing physiology and pathophysiology, because other proteins could still play an essential role.

Item Type:	Thesis (Thesis)
Supervisor name:	Pyott, Sonja PhD and UMCG, Department of Otorhinolaryngology and and Head and Neck Surgery
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:50
Last Modified:	25 Jun 2020 10:50
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/1126

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