Perturbing the Active Process of Hair Cells: Self Recovery of Spontaneous Oscillations Following Overstimulation

Abstract

In the inner ear, hair cells perform the transduction of mechanical input into electrical output. An energy-consuming process enhances their sensitivity to incoming auditory and vestibular stimuli. One manifestation of this active process is spontaneous oscillation of the mechano-sensitive organelle, the hair bundle, which is at the apical surface of each hair cell. To attain this increased sensitivity, the hair bundle is postulated to operate near a bifurcation, where an internal control parameter vital to the active process determines whether the bundle shows limit cycle oscillations or is quiescent. This control parameter may be linked to adaptation in vertebrate hair cells and could help explain how prolonged high-level sounds cause a temporary threshold shift in mammalian hearing. High amplitude, prolonged deflection of bullfrog sacculus bundles have been shown to temporarily suppress spontaneous oscillations, suggesting a readjustment of the control parameter through a bifurcation. The transition back from quiescence to limit cycle oscillations has been shown to depend on the duration of the imposed deflection and on calcium ion concentration around the mechanically gated transduction channels.Here, we present experiments where we identify other environmental factors that affect this control of the active process. We introduce various pharmacological agents to manipulate the mechano-sensitive transduction channels and the myosin motors inside the hair bundles. We compare how these agents affect particular components of the internal control parameter by measuring the duration of the induced quiescent intervals and the time scales associated with the return of the bundle's position to equilibrium. Additionally, we attach magnetic bead particles to the hair bundles and deflect with a strong magnetic field. Thus, hair bundles avoid physical contact with the stimulus probe, and experience no external hydrodynamic effects. Selected results are discussed.