Abstract 105, Date 1:00 pm, Sunday, February 11, 2007 (24 hours) Session D3: Poster
In Vivo Effects of Reduced-Sodium Perilymph Perfusion on Hair Cell and Neural Potentials
*Greg A. O'Beirne, Robert B. Patuzzi
To determine the functional significance of the sodium-transport mechanisms of the OHCs in vivo, the effect of reduced perilymphatic sodium on cochlear potentials was investigated by perfusion of scala tympani with a modified artificial perilymph. The Na+ concentration of the artificial perilymph was reduced by almost 95% (from 150 mM to 8 mM) by substitution with choline, and resulted in an estimated 80% reduction in perilymphatic Na+ on perfusion through scala tympani. OHC function was assessed using Boltzmann analysis of the low-frequency CM and measurement of the high-frequency summating potential recorded at the round window. Neural thresholds and waveforms were monitored at multiple frequencies. To ensure that the observed effects were due to the reduced Na+ concentration rather than direct action of choline, experiments were conducted that employed i) pre- and co-perfusion with the nicotinic ACh receptor antagonist hexamethonium chloride, and ii) the use of NMDG+ instead of choline to replace Na+. The >10 minute perfusions caused a transient 2-6% increase in the maximal CM amplitude, a 6-15% increase in MET sensitivity, and a small operating-point shift towards scala tympani that was followed by a larger sustained shift in the opposite direction. These effects were found to be reproducible and reversible, and were largely consistent with an increase in OHC cytosolic Ca2+ concentration due to a reduction in Ca2+ efflux through the Na+/Ca2+ antiport (Ikeda et al., 1992). The use of NMDG+ as the Na+-substitution ion produced similar effects to the choline, and blockade of the ACh-sensitive Ca2+ channels of the OHCs by hexamethonium produced no difference in the effects observed. Reductions in the amplitude of the CAP and spontaneous neural noise indicated a distinct neural effect in addition to the hair cell effects. The experimental results from the guinea pig are compared with simulated perfusions carried out in a mathematical model of cochlear regulation.