Calcium entry does not drive fast mechanotransduction adaptation in cochlear hair cells
Sound detection in auditory sensory hair cells depends on the deflection of the stereocilia hair bundle, which opens mechano-electric transduction (MET) channels. Adaptation is hypothesized to be a critical property of MET that contributes to the wide dynamic range and sharp frequency selectivity of the auditory system. Historically, adaptation was hypothesized to have multiple mechanisms, all of which require calcium entry through MET channels. Our recent work using a stiff probe to displace
... probe to displace hair bundles showed that the fastest adaptation mechanism (fast adaptation) does not require calcium entry. Using a fluid jet stimulus, others obtained data showing only a calcium-dependent fast adaptation response. Here, we identified the source of this discrepancy. Because the hair cell response to a hair bundle stimulus depends critically on the magnitude and time course of the hair bundle deflection, we developed a high-speed imaging technique to quantify this deflection. The fluid jet delivers a force stimulus, and step-like force stimuli lead to a complex time course of hair bundle displacement (mechanical creep), which affects the hair cell's macroscopic MET current response by masking the time course of the fast adaptation response. Modifying the fluid-jet stimulus to generate a step-like hair bundle displacement produced rapidly adapting currents that did not depend on membrane potential. This indicated that fast adaptation does not depend on calcium entry. We also confirmed the presence of a calcium-dependent slow adaptation process. These results confirm the existence of multiple adaptation processes: a fast adaptation that is not driven by calcium entry and a slower calcium-dependent process.