Proceedings of The Physiological Society

Physiology 2014 (London, UK) (2014) Proc Physiol Soc 31, PCB074

Poster Communications

Mechanotransducer Channel Properties of Outer Hair Cells are Altered in the tmc1 Mutant Mouse, Beethoven

L. F. Corns1, W. Marcotti1

1. Biomedical Sciences, University of Sheffield, Sheffield, United Kingdom.


The mechanotransducer (MET) channel opens in response to stereociliary bundle deflection resulting in an inward current which depolarises hair cells and drives synaptic transmission at their basolateral membrane. Despite the importance of this channel the molecular identity is unknown, although a strong candidate is TMC1. Tmc1 mutations in humans cause progressive hearing loss which can be modelled by the mutant mouse, Beethoven (tmc1bth/bth; Vreugde et al., 2002). Beethoven mice have a single point mutation in tmc1, with deafness phenotypes observed in tmc1bth/+ mice and tmc1bth/bth mice. Studying the MET current in these mice allows us to investigate integral channel properties. This allows us to provide more evidence as to whether TMC1 is a component of the channel or is performing another function such as trafficking or a role in development. Organs of Corti were acutely dissected (see Marcotti et al., 2006 for details) from Beethoven mice and their wild-type littermates which are bred on a C3HeB/FeJ background. Whole cell patch clamp recordings were made from outer hair cells (OHCs) of both the apical and basal coil for a range of ages from postnatal day 4 (P4) to P14. To elicit the MET current, a piezoelectric driven fluid jet was placed close to the hair bundles and sinusoidal stimuli applied (50 Hz). The MET current reversal potential, an indication of calcium permeability of the MET channel, was recorded as described previously (Kim & Fettiplace, 2013). Data are expressed as mean ± S.E and statistical significance was determined using a one-way ANOVA with post-hoc Bonferroni tests. The amplitude of the MET currents recorded in apical OHCs from tmc1bth/+ and tmc1bth/bth mice were similar to those observed in wild-type littermates. Despite this lack of change in the maximal current amplitude, we found significant differences in the reversal potential of the MET channel in both tmc1bth/+ and tmc1bth/bth compared to their wild-type littermates. For apical OHCs the reversal potentials were 25.4 mV ± 0.4 (n = 5), 16.9 mV ± 0.7 (n = 10) and 12.5 mV ± 1.7 (n = 6) for tmc1+/+, tmc1bth/+ and tmc1bth/bth, respectively. For basal OHCs the reversal potentials were 26.2 mV ± 0.8 (n = 2), 15.0 mV ± 0.5 (n = 11) and 11.3 mV ± 0.4 (n = 8) for tmc1+/+, tmc1bth/+ and tmc1bth/bth, respectively. The ability of a mutation in tmc1 to modify a pore property of the MET channel does suggest that it could be a component of the transducer channel, substantiating recent results in inner hair cells of tmc1bth/+/tmc2-/- mice (Pan et al., 2013) and OHCs in deafness (tmc1-/-) mice (Kim & Fettiplace, 2012). Nevertheless, the possibility that TMC1 could be playing another role within hair cells cannot be excluded.

Where applicable, experiments conform with Society ethical requirements