Stereocilium height changes can account for the calcium dependence of the outer-hair-cell bundle's resting state

Abstract

Outer-hair-cell bundles are sensory organelles required for normal hearing in mammals. These bundles convert sound-induced forces into receptor currents. This conversion depends on the resting receptor current of each bundle, which increases when extracellular calcium is decreased to the physiological level. How extracellular calcium regulates the bundles resting state is not well understood. We propose a mechanism explaining how extracellular calcium can regulate the outer-hair-cell bundles resting state. Each bundle comprises filamentous stereocilia linked by gating springs that are attached to ion channels. Sound-induced forces deflect stereocilia, increasing and decreasing gating-spring tensions, opening and closing the ion channels, resulting in an oscillating receptor current. We hypothesize that decreasing extracellular calcium, decreases the heights of the shorter stereocilia, increasing resting gating-spring tensions, which increases the resting receptor current and decreases the bundles resting deflection. To determine the plausibility of this mechanism, we build a mathematical model of an outer-hair-cell bundle and calibrate the model using seven independent experimental observations. The calibrated model shows that the mechanism is quantitatively plausible and predicts that a decrease of only 10 nm in the heights of the shorter stereocilia when extracellular calcium is lowered is sufficient to explain the observed increase in the resting receptor current. The model predicts the values of nine parameters and makes several additional predictions.