Professor, Department of Neuroscience
Ph.D. University of Cambridge
Transduction and Turning in Hair Cells of the Inner Ear
My research is concerned with the hair cells of the inner ear, sensory receptors which convert sound into an electrical signal and also analyze its frequency constituents. Hair cells detect sound through deflection of a bundle of modified microvilli known as stereocilia thereby activating mechanically-sensitive (MS) ion channels. Ion flux through the MS channel causes a receptor potential that in turn controls neurotransmitter release onto second order auditory neurons. My work has employed patch clamp recording and optical imaging to provide descriptions of the transduction mechanism, the ion channels involved in frequency tuning, and the roles of intracellular calcium. Various facets of my research have involved development or new use of imaging techniques including dual or array photodiodes for detecting nanometer motion and measuring hair cell mechanics, real time and swept field confocal microscopy with fast kHz-frame CCD cameras for quantifying rapid local changes in calcium. I have recently focused on the MS channels of mammalian cochlear hair cells. Surprisingly, the molecular identity of the MS channel is still unknown but over the last ten years we have characterized its properties in detail for comparison with putative channel proteins and are now on the verge of confirming its identity. Using fast calcium imaging, we demonstrated that the MS channels are localized to the top of each stereocilium. We also found that these channels in different types of hair cells have different single-channel conductance and permeability calcium. The differences appear to be specified by ‘transmembrane channel-like’ (TMC) proteins, and can be abrogated by gene knockouts of TMC1 or TMC2. Mutations of TMC1 are known to be linked to profound or progressive hearing loss in both humans and mice.
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