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Volume 16, Number 16,
Issue of August 15, 1996
pp. 4881-4889
Copyright ©1996 Society for Neuroscience
Effects of Salicylate and Lanthanides on Outer Hair Cell Motility
and Associated Gating Charge
Received March 26, 1996; revised May 16, 1996; accepted May 21, 1996.
Seiji Kakehata and
Joseph Santos-Sacchi
Sections of Otolaryngology and Neurobiology, Yale University School
of Medicine, New Haven, Connecticut 06510
Salicylate, one of the most widely used drugs, is known to induce
reversible tinnitus and hearing loss. Salicylate interferes with outer
hair cells (OHCs), which are believed to underlie normal auditory
frequency selectivity and sensitivity. In the present experiments, the
effects of salicylate and lanthanides on OHC motility and nonlinear
capacitance were investigated by using isolated guinea-pig OHCs while
attempting to avoid inadvertent intracellular pressure change, which
itself can affect OHC motility and capacitance. Either extracellularly
or intracellularly applied salicylate reduced nonlinear peak
capacitance (Cmpk) and shifted the voltage
at peak capacitance to depolarized levels. Concentration-response
curves for reduction in Cmpk by salicylate
and GdCl3 revealed a half-maximal concentration
and Hill coefficient of 1.6 mM and 1.0, and 0.6 mM and 1.2, respectively. In comparable groups of
OHCs, the normal Cmpk values of which were
near 40 pF, average Cmpk decreased to 28 and 36 pF for intracellularly and extracellularly applied salicylate,
respectively. Salicylate reduced, but did not completely block, the
voltage-induced length change. Extracellularly, but not
intracellularly, applied lanthanide blocked voltage-induced movement
and capacitance almost completely. After intracellular trypsin
treatment, salicylate reduced voltage-dependent capacitance reversibly,
suggesting that salicylate directly acts on the sensor/motor and not
via effects on intracellular structures, such as the subsurface
cisternae. The results are consistent with the hypothesis that the
dissociated, charged form of salicylate directly interacts with the
sensor/motor on the inner aspect of the OHC plasma, whereas lanthanides
interact on the outer aspect.
Key words:
outer hair cell;
salicylate;
motility;
nonlinear
capacitance;
gating currents;
lanthanides
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