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Published on: February 8, 2020
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LRRC52 regulates BK channel function and localization in mouse cochlear inner hair cells
Christopher J Lingle1, Pedro L Martinez-Espinosa2, Aizhen Yang-Hood3
1Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110; clingle@morpheus.wustl.edu rutherfordmark@wustl.edu.
Summary
The leucine-rich-repeat-containing 52 (LRRC52) subunit is crucial for the function and localization of calcium-activated potassium (BK) channels in auditory hair cells. Its absence significantly alters BK channel activation and positioning, impacting sound perception.
Area of Science:
- Neuroscience
- Auditory Physiology
- Molecular Biology
Background:
- Sound perception depends on cochlear hair cells converting mechanical energy into neural signals via glutamate release.
- Voltage-dependent conductances, particularly calcium-activated potassium (BK) channels, shape hair cell receptor potentials and synaptic transmission.
- Mammalian inner hair cells (IHCs) exhibit unusual BK channel properties, including activation at negative potentials and distinct localization.
Purpose of the Study:
- To investigate the roles of LRRC26 and LRRC52 regulatory subunits in BK channel function and localization within mouse IHCs.
- To determine the impact of LRRC26 and LRRC52 absence on BK channel gating and positioning.
Main Methods:
- Utilized knockout (KO) mouse models for Lrrc26 and Lrrc52.
- Electrophysiological recordings to measure BK currents in IHCs.
- Microscopy techniques to assess BK channel localization.
Main Results:
- Loss of LRRC26 did not affect BK currents or channel localization in IHCs.
- Lrrc52 KO mice exhibited a significant positive shift (> +200 mV) in BK current activation.
- Absence of LRRC52 disrupted BK channel localization in IHCs.
Conclusions:
- LRRC52 plays a critical role in determining the activation range and proper positioning of BK channels in IHCs.
- While LRRC52 coexpression shifts BK gating negatively (-90 mV), additional factors likely contribute to the full activation range observed in IHCs.
- LRRC52 may stabilize a macromolecular complex essential for negative potential BK channel activation and localization.
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