Background: In mammals, a specialized auditory end organ, the Organ of Corti, is responsible for hearing. It comprises supporting cells and secondary sensory cells (inner IHC; and outer hair cells OHC). IHCs and OHCs employ mechano-electrical transduction (MET) to translate sound in electrical signals. Their sensory organelle, the hair bundle, is comprised of three rows of stereocilia, that are arranged in a staircase pattern. Deflections towards the tallest row activate MET channels. While non-auditory MET channels (such as TRAK1) can be activated or modulated by changes to their lipid environment, these interactions for mammalian auditory MET channel remain uninvestigated. Additionally, some lipid metabolism diseases lead to hearing loss/impairment, as does treatment with aminoglycosides.

Methods: We used g-cyclodextrin to extract lipids and methyl-b-cyclodextrin to extract cholesterol form the membrane, while simultaneously recording the MET current of IHC and OHC during stimulation with a piezo driven stiff probe.

Results: Non-selective lipid extraction reversibly reduced the peak MET current, current adaptation, and decreased the number of channels open at rest. The recovery after g-cyclodextrin treatment took longer than the onset of the effects, suggesting that a specific lipid organization is required for MET channel function. Extraction of cholesterol, using Mb-cyclodextrin, irreversibly reduces the peak MET current and reversibly increases the channel resting open probability, suggesting that cholesterol restricts MET channel opening.

Conclusion: Together this data suggests that the cell membrane is part of the force relay machinery to the MET channel and could possibly restrict gating associated conformational changes of the MET channel.

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