Direct recording of mechano-electrical transduction currents and forces from individual stereocilia
Year of award: 2015
Grantholders
Dr Andriy Kozlov
Imperial College London
Project summary
Mechano-electrical transduction (MET) in the inner ear occurs when a sound's energy is transmitted to MET channels in the hair-cell stereocilia. The gating of channels and stereocilia motion are directly and reciprocally coupled. This mechanical coupling involves tip links which are molecular springs whose tension determines the channels’ open probability. Pulling on a tip link opens a channel and this relaxes the spring. This relaxation, called gating compliance, involves channel motions exceeding a dozen nanometres – astoundingly large for an ion channel. Classical models suggest there is one MET channel connected to a tip link's upper end.
Recent experiments reveal 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 open and close cooperatively. Large gating compliance arises naturally in my model, provided the channels are at the tip link's lower end. This collaborative project will quantify the MET-channel cooperativity and the associated gating compliance using two new methods – a single-stereocilia patch clamp and single-tip-link microrheology.