Auditory transduction begins when sound-induced vibrations are converted into electrical signals by opening mechanotransducer (MT) channels in cochlear hair cells. Although the molecular composition of the MT channel is not yet firmly established, the transmembrane channel-like (Tmc) protein isoforms 1 and 2 have received recent attention. This study characterized MT currents using whole-cell patch recordings in neonatal outer hair cells (OHCs) and inner hair cells (IHCs) of wild type and Tmc mutant mice. The properties of MT currents were documented at different locations along the cochlea's tonotopic axis. The results showed that: (1) MT current amplitude increased and the channel Ca2+ permeability decreased from the cochlear apex to base in OHCs but not in IHCs of wild type neonates; (2) OHC MT currents in Tmc1 knockout mice developed normally but declined to zero after the first week, which may explain the deafness phenotype; (3) the MT channel Ca2+ permeability was larger in Tmc1 knockouts in OHCs and smaller in Tmc2 knockouts of both OHCs and IHCs; (4) MT single-channel conductance increased from apex to base in wild-type OHCs, was similar in Tmc2 knockouts but was smaller in Tmc1 knockouts. These findings lead to the conclusion that Tmc1 and Tmc2 regulate the Ca2+ permeability of the MT channel and may form part of the MT channel complex. Recordings in Tmc1/Tmc2 double knockouts revealed a third channel type with distinct Ca2+ permeability and responsiveness that suggested another subunit.
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