Mechano-elektrische Transduktionsströme in auditorischen Haarzellen von Ratten werden durch Cholesterin in der Zellmembran moduliert

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). The cells employ mechano-electrical transduction (MET) to translate sound to electr-chemical signals. Their sensory organelle, the hair bundle, harbors the MET channels at the tip of the shorter two of in total three rows of stereocilia, that are arranged in a staircase pattern. Deflections towards the tallest row activate MET channels. How these mammalian auditory MET channels depend on the cholesterol content of their surrounding cell membrane remains unknown. However, some cholesterol metabolism diseases, such as Niemann-Picks disease or Smith-Lemli-Opitz-Syndrome also lead to hearing loss/impairment.

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

Results: Extraction of cholesterol, using MbCD, irreversibly reduces the peak MET current, at high concentrations (>10 mM) and reversibly increases the channel resting open probability (at concentrations from 3-50 mM), suggesting that cholesterol restricts MET channel opening. Depletion also affects the extent of adaptation (measured as the currents returning to baseline during constant stimulation) and the speed of adaptation.

Conclusion: Together this data suggests that the cell membrane is part of the force relay machinery to the MET channel and possibly also restricts channel conformation changes.

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