Description:

Hair cells of both the auditory and vestibular systems use calcium to control aspects of performance and tuning. Self-referencing Ca²⁺ ISEs have been used to follow the role of the plasma membrane Ca²⁺/H⁺ ATPase (PMCA) in the regulation of this flux. A substantial calcium efflux could be measured, suggesting, in conjunction with pump density, that the PMCA activity should generate a substantial membrane current as the bundles expel cytosolic Ca²⁺. As nitric oxide synthase is localized in the efferent nerve terminals of the mammalian inner ear we hypothesized that nitric oxide (NO) acts to modulate both calcium and potassium currents and thus the gain of the hair cell's activity profile. Currently we have focussed on the calcium conductance.

Progress:

Using the NO design of self-referencing sensor developed at the BioCurrents Research Center we have shown:

1. Acetylcholine, the putative efferent nerotransmitter, releases NO from the saccula.

2. NO applied in solutions reduced the whole cell Ca²⁺ currents as well as the single channel Ca²⁺ current in hair cells.

3. Reduced Ca²⁺ conductance results from cells held in the open probability state.

4. The effects of NO are reversible using dithiothreitol. We conclude that by reducing the Ca²⁺ influx and decreasing neurotransmitter release, NO modulates the gain of the hair cell.