Direct recording of mechano-electrical transduction currents and forces from individual stereocilia. (360G-Wellcome-108034_Z_15_Z)

£100,000

Mechano-electrical transduction (MET) in the inner ear occurs when a sound's energy is transmitted to MET channels in the hair-cell stereocilia. Channels' gating and stereocilia motion are directly and reciprocally coupled. This mechanical coupling involves tip links--molecular springs whose tension determines the channels' open probability. Pulling on a tip link opens a channel; channel opening relaxes the spring. This relaxation, called gating compliance, involves channel motions exceeding a d ozen nanometres, astoundingly large for an ion channel. Classical models posit one MET channel connected to a tip link's upper end. Recent experiments reveal instead two channels at a tip link's lower end. No model today can explain the number and location of the MET channels, nor how the large gating compliance, necessary for sensitive hearing, occurs. I propose that adjacent MET channels are energetically coupled through elastic deformations they create in the lipid bilayer, and that they ther efore open and close cooperatively. Large gating compliance arises naturally in my model, provided the channels are at the tip link's lower end. To quantify the MET-channel cooperativity and the associated gating compliance requires new methods: single-stereocilia patch clamp and single-tip-link microrheology. This collaborative project's objective is to develop these methods.

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Grant Details

Amount Awarded 100000
Applicant Surname Kozlov
Approval Committee ERG2 Cellular and Molecular Neuroscience
Award Date 2015-04-30T00:00:00+00:00
Financial Year 2014/15
Grant Programme: Title Seed Award in Science
Internal ID 108034/Z/15/Z
Lead Applicant Dr Andrei Kozlov
Partnership Value 100000
Planned Dates: End Date 2017-08-31T00:00:00+00:00
Planned Dates: Start Date 2015-09-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London