Thyroid hormone receptor alpha1 is a critical regulator for the expression of ion channels during final differentiation of outer hair cells.

Cochlear outer hair cells (OHCs) terminally differentiate prior to the onset of hearing. During this time period, thyroid hormone (TH) dramatically influences inner ear development. It has been shown recently that TH enhances the expression of the motor protein prestin via liganded TH receptor beta (TRbeta) while in contrast the expression of the potassium channel KCNQ4 is repressed by unliganded TRalpha1. These different mechanisms of TH regulation by TRalpha1 or TRbeta prompted us to analyse other ion channels that are required for the final differentiation of OHCs. We analysed the onset of expression of the Ca(2+) channel Ca(V)1.3, and the K(+) channels SK2 and BK and correlated the results with the regulation via TRalpha1 or TRbeta. The data support the hypothesis that proteins expressed in rodents prior to or briefly after birth like Ca(V)1.3 and prestin are either independent of TH (e.g. Ca(V)1.3) or enhanced through TRbeta (e.g. prestin). In contrast, proteins expressed in rodents later than P6 like KCNQ4 ( approximately P6), SK2 ( approximately P9) and BK ( approximately P11) are repressed through TRalpha1. We hypothesise that the precise regulation of expression of the latter genes requires a critical local TH level to overcome the TRalpha1 repression.