Steady-State Adaptation of Mechanotransduction Modulates the Resting Potential of Auditory Hair Cells, Providing an Assay for Endolymph [Ca²⁺]

Abstract

The auditory hair cell resting potential is critical for proper translation of acoustic signals to the CNS, because it determines their filtering properties, their ability to respond to stimuli of both polarities, and, because the hair cell drives afferent firing rates, the resting potential dictates spontaneous transmitter release. In turtle auditory hair cells, the filtering properties are established by the interactions between BK calcium-activated potassium channels and an L-type calcium channel (electrical resonance). However, both theoretical and in vitro recordings indicate that a third conductance is required to set the resting potential to a point on the I Ca and I BK activation curves in which filtering is optimized like that found in vivo. Present data elucidate a novel mechanism, likely universal among hair cells, in which mechanoelectric transduction (MET) and its calcium-dependent adaptation provide the depolarizing current to establish the hair cell resting potential. First, mechanical block of the MET current hyperpolarized the membrane potential, resulting in broadband asymmetrical resonance. Second, altering steady-state adaptation by altering the [Ca 2ϩ ] bathing the hair bundle changed the MET current at rest, the magnitude of which resulted in membrane potential changes that encompassed the best resonant voltage. The Ca 2ϩ sensitivity of adaptation allowed for the first physiological estimate of endolymphatic Ca 2ϩ near the MET channel (56 Ϯ 11 M), a value similar to bulk endolymph levels. These effects of MET current on resting potential were independently confirmed using a theoretical model of electrical resonance that included the steady-state MET conductance.

Organ of Corti and Stria Vascularis: Is there an Interdependence for Survival?

“…Hair cell loss is considered for this elevation. In the normal cochlea, there is a standing (leak) current through mechanotransduction channels at rest [66,67]. This current reduces the voltage difference between the scala media and scala tympani [68].…”

Linear and nonlinear processing in hair cells

“…This phenomenon has been studied most extensively in the turtle cochlea, where small positive and negative current steps evoke symmetrical voltage oscillations around the resting potential that scale with the step amplitude. The resting transduction current caused by the slow mechanical adaptation described above may be an important factor in depolarizing V m into this linear operating range (Farris et al, 2006). V m also influences adaptation through its effect on Ca influx.…”

Calcium-dependent Binding of HCN1 Channel Protein to Hair Cell Stereociliary Tip Link Protein Protocadherin 15 CD3

“…cAMP-gated I h , possibly in addition to the mechanosensory-transduction current, sets the membrane potential for a subpopulation of saccular hair cells (2,3). The membrane potential in the saccular hair cell subpopulation is sufficiently depolarized to activate voltage-gated calcium channels, permitting influx of calcium and secretion of hair cell transmitter (2).…”