Nitrosoglutathione suppresses cochlear potentials and DPOAEs but not outer hair cell currents or voltage-dependent capacitance.
Biochemical and pharmacological evidence support a role for nitric oxide (NO) and glutathione (GSH) in the cochlea. GSH combines with NO in tissue to form nitrosoglutathione (GSNO) that can act as a storage form for GSH and NO. Therefore, we tested GSNO on sound-evoked responses of the cochlea (cochlear microphonic, CM; summating potential, SP; compound action potential, CAP; cubic distortion product otoacoustic emission, DPOAE), on the endocochlear potential (EP), on isolated outer hair cell (OHC) currents and voltage-dependent capacitance, and on Deiters' cell currents. In vivo application of GSNO in increasing concentrations reversibly reduced low-intensity sound-evoked CAP, SP and DPOAEs starting at about 1 mM (CAP) and 3.3 mM (SP, DPOAE). However, even at 10 mM, GSNO had little effect on the EP. In vitro, salicylate (10 mM) but not GSNO (3 and 10 mM) suppressed the early capacitative transients of OHCs. GSNO (3 and 10 mM) had no effect on the whole cell currents of OHCs or Deiters' cells. Results show that GSNO suppresses cochlear function. This suppression may be due to an effect of GSNO on the cochlear amplifier. The actions of GSNO were different from those of other NO donors; therefore, the effects of GSNO may not be mediated by NO. The mechanisms underlying GSNO effects seem to be different from those of salicylate.
Nenov
A P
AP
Kresge Hearing Research Laboratory of the South, Department of Otorhinolaryngology and Biocommunication, Louisiana State University Medical Center, New Orleans 70112-2234, USA.
Skellett
R A
RA
Fallon
M
M
Bobbin
R P
RP
D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D002469:Cell Separation; D003051:Cochlea / Q000187:drug effects / Q000502:physiology; D003055:Cochlear Microphonic Potentials / Q000187:drug effects*; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D009603:Nitroso Compounds / Q000494:pharmacology*; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D026422:S-Nitrosoglutathione; D000159:Vestibulocochlear Nerve / Q000187:drug effects / Q000502:physiology
D009603:Nitroso Compounds; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D005978:Glutathione