On the temperature and tension dependence of the outer hair cell lateral membrane conductance GmetL and its relation to prestin.

Recently, we identified an outer hair cell (OHC) lateral membrane conductance, GmetL, that colocalizes with prestin and passes Cl-, thereby influencing prestin's (SLC26A5) electromechanical activity. In this study, we report on a comparison of the temperature and tension dependence of GmetL and prestin. Though we find significant temperature and tension dependence of each, substantial differences exist which indicate their independent identity. The following data support this conclusion: (1) The voltage dependence of GmetL does not follow that of prestin's nonlinear capacitance (NLC) function when the latter is shifted by either temperature or membrane tension; (2) Unlike native OHCs whose NLC can be modulated by influx of extracellular Cl-, prestin-transfected Chinese hamster ovary (CHO) cells do not show this phenomenon; (3) Stretch-sensitive, single channel currents are not evidenced after prestin transfection in CHO cells; and (4) There is no correlation between prestin expression level (gauged via NLC) and transmembrane current through GmetL. Thus, GmetL must result from the activity of another molecular species within the lateral membrane of the OHC. A clue to its identity is the conductance's nonlinear temperature dependence in contrast to prestin and other OHC conductances' linear dependence. Whereas K+ conductances in OHCs present a uniform Q10 close to 1.2, GmetL shows a bimodal Q10, with a Q10 of 1.5 below 34 degrees C and a Q10 of greater than 4 and above. The dissociation of SLC26A5 (prestin) and GmetL theoretically provides for a modifiable anionic feedback to prestin via the degree of spatial separation between these interacting partners within the OHC lateral membrane.