Voltage-Mediated Control of Spontaneous Bundle Oscillations in Saccular Hair Cells

Abstract

Hair cells of the vertebrate vestibular and auditory systems convert mechanical inputs into electrical signals that are relayed to the brain. This transduction involves mechanically gated ion channels that open following the deflection of mechanoreceptive hair bundles that reside on top of these cells. The mechano-electrical transduction includes one or more active feedback mechanisms to keep the mechanically gated ion channels in their most sensitive operating range. Coupling between the gating of the mechanosensitive ion channels and this adaptation mechanism leads to the occurrence of spontaneous limit-cycle oscillations, which indeed have been observed in vitro in hair cells from the frog sacculus and the turtle basilar papilla. We obtained simultaneous optical and electrophysiological recordings from bullfrog saccular hair cells with such spontaneously oscillating hair bundles. The spontaneous bundle oscillations allowed us to characterize several properties of mechano-electrical transduction without artificial loading the hair bundle with a mechanical stimulus probe. We show that the membrane potential of the hair cell can modulate or fully suppress innate oscillations, thus controlling the dynamic state of the bundle. We further demonstrate that this control is exerted by affecting the internal calcium concentration, which sets the resting open probability of the mechanosensitive channels. The auditory and vestibular systems could use the membrane potential of hair cells, possibly controlled via efferent innervation, to tune the dynamic states of the cells.

Synchronization of Spontaneous Active Motility of Hair Cell Bundles

“…Bundles were found to oscillate at comparable amplitudes under coupled and uncoupled conditions. Since spontaneous oscillation was shown to correlate closely with opening and closing of the transduction channels [ 41 ], the presence of the microsphere did not significantly interfere with the transduction process.…”

Effects of Efferent Activity on Hair Bundle Mechanics

“…Transepithelial electrical stimulation was shown to trigger and entrain active bundle motility (Bozovic and Hudspeth, 2003). A combination of cell electrophysiology and mechanical bundle manipulation likewise demonstrated that membrane potential impacts active motility (Meenderink et al, 2015). Steady-state changes in the membrane potential were found to modulate the frequency, amplitude, and shape of spontaneous oscillations.…”

Nonequilibrium limit-cycle oscillators: Fluctuations in hair bundle dynamics

“…Typical recordings are limited to observations of hair bundle mechanics, its oscillation and response to an imposed drive. Recently, recordings of bundle mechanics were combined with electrophysiological recordings of the cell soma, in spontaneously oscillating and driven bundles [40]. This technique allows the simultaneous probing of two variables, the hair bundle position X and the cell membrane potential V ss .…”

“…These recording conditions maintain the innate bundle oscillations, while providing access to the electrical state of the cell. These measurements were made in current-clamp mode, yielding data on the time-varying membrane potential [40]. The time delay in the voltage recording, due to the pipette resistance and the hair cell capacitance was on the order of ∼1 -2 ms. We neglect this in comparison to the bundle's time period ∼30 ms.…”