Action of salicylate on membrane capacitance of outer hair cells from the guinea-pig cochlea.
1. The effect of salicylate on membrane capacitance and intracellular pH has been measured in isolated outer hair cells (OHCs) during whole cell recording. Cell membrane capacitance was measured using a lock-in amplifier technique. 2. Salicylate applied in the bath reduced the fast charge movement, equivalent to a voltage-dependent membrane capacitance, present in OHCs. Simultaneous measurement of membrane capacitance and voltage-driven cell length changes showed that salicylate reduced both together. 3. A small effect of salicylate on outward currents at 0 mV was observed. Sodium salicylate (5 mM) reduced the currents by 19% and another weak acid, sodium butyrate (10 mM), reduced outward currents in OHCs by 15%. 4. The ratiometric dye 2,7-bis(2-carboxymethyl)-5,6-carboxyfluorescein (BCECF) was used to measure pHi changes in OHCs during weak acid exposure. Membrane capacitance and pHi were measured simultaneously in OHCs exposed first to 10 mM sodium butyrate and then to 5 mM sodium salicylate. Although both compounds produced a similar reduction in pHi, butyrate decreased the resting capacitance from a mean resting capacitance of 35 pF (at -30 mV) by 5.4 +/- 2.1 pF, whereas salicylate decreased it by 15.7 +/- 2.3 pF (n = 4). 5. Exposure of OHCs to 10 mM sodium benzoate, an amphiphilic anion, reduced resting membrane capacitance at -30 mV by 9.2 +/- 3.2 pF (n = 3). Outward currents, measured at 0 mV, were reduced by 0.25 +/- 0.05 nA during benzoate application, comparable with the effect of salicylate. 6. Capacitance was measured during slow bath application of salicylate. The resulting dose-capacitance curve had a Hill coefficient of 3.40 +/- 0.85 (n = 4) and a half-maximal dose of 3.95 +/- 0.34 mM. The dose-capacitance curve was not significantly voltage dependent. 7. Salicylate had no detectable effect on the resting capacitance of Deiters' cells, a non-sensory cell type of the organ of Corti. 8. It is concluded that many of the described effects of salicylate on hearing may arise from the partitioning of the salicylate molecule into the membrane of the OHC and consequent inhibition of OHC motility.
Tunstall
M J
MJ
Department of Physiology, School of Medical Sciences, University of Bristol, UK.
Gale
J E
JE
Ashmore
J F
JF
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D019817:Benzoic Acid; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D003600:Cytosol / Q000187:drug effects / Q000502:physiology; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D012459:Salicylates / Q000494:pharmacology*; D020156:Salicylic Acid
D001565:Benzoates; D002087:Butyrates; D005452:Fluoresceins; D005456:Fluorescent Dyes; D012459:Salicylates; D020148:Butyric Acid; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; D019817:Benzoic Acid; D020156:Salicylic Acid