A four-state kinetic model of the temporary threshold shift after loud sound based on inactivation of hair cell transduction channels.

A model of the temporary threshold shift (TTS) following loud sound is presented based on inactivation of the mechano-electrical transduction (MET) channels at the apex of the outer hair cells (OHCs). This inactivation is assumed to reduce temporarily the OHC receptor current with a consequent drop in the mechanical sensitivity of the organ of Corti. With acoustic over-stimulation some of the hair cells' MET channels are assumed to adopt one of three closed and non-transducing conformations or 'TTS states'. The sound-induced inactivation is assumed to occur because the sound makes the TTS states more energetically favourable when compared with the transducing states, and the distribution between these states is assumed to depend on the relative energies of the states and the time allowed for migration between them. By lumping the fast transducing states (one open and two closed) into a single transducing 'pseudo-state', the kinetics of the inactivation and re-activation processes (corresponding to the onset and recovery of TTS) can be described by a four-state kinetic model. The model allows an elegant description of the onset and recovery of TTS time-course in a human subject under a variety of continuous exposure conditions, and some features of intermittent exposure as well. The model also suggests that recovery of TTS may be accelerated by an intermittent tone during the recovery period which may explain some variability TTS in the literature. Other implications of the model are also discussed.