Gating energies and forces of the mammalian hair cell transducer channel and related hair bundle mechanics

We quantified the molecular energies and forces involved in opening and clo sing of mechanoelectrical transducer channels in hair cells using a novel g enerally applicable method. It relies on a thermodynamic description of the free energy of an ion channel in terms of its open probability. The molecu lar gating force per channel as reflected in hair bundle mechanics is shown to equal kT/I(X) x dI(X)/dX, where I is the transducer current and X the d eflection of the hair bundle. We applied the method to previously measured I(X) curves in mouse outer hair cells (OHCs) and vestibular hair cells (VHC s). Contrary to current models of transduction, gating of the transducer ch annel was found to involve only a finite range of flee energy (< 10 kT), a consequence of our observation that the channel has a finite minimum open p robability of ca. 1% for inhibitory bundle deflections. The maximum gating forces per channel of both cell types were found to be comparable (ca. 300- 500 fN). Because of differences in passive restoring forces, gating forces result in very limited mechanical nonlinearity in OHC bundles compared to t hat in VHC bundles. A kinetic model of channel activation is proposed that accounts for the observed transducer currents and gating forces. It also pr edicts adaptation-like effects and spontaneous bundle movements ensuing fro m changes in state energy gaps possibly related to interactions of the chan nel with calcium ions.