Robert Fettiplace, Ph.D.
Waisman Center @ 8:30 am - 9:30 am
Learn more about the Hearing and Donuts Seminar Series
Sound transduction in cochlear hair cells arises by activation of mechanotransducer channels composed primarily of transmembrane channel-like protein 1 (TMC1). We have found that mutations in Tmc1 cause hair cell death and deafness in mice by postnatal day 21. However, mechano-transduction is normal in the first postnatal week. Our goal is to understand what triggers apoptosis, death of the hair cells, and deafness in these mouse mutants. I shall show that in all Tmc1 mutants studied, there was a reduction in the density of the PMCA2 Ca2+ pump in the outer hair cell stereocilia. This leads to an increase in cytoplasmic Ca2+ which deleteriously affects mitochondrial function. The results imply a connection between stereociliary PMCA2 density, hair cell apoptosis and deafness.





