Potassium ion channel openers, Maxipost and Retigabine, protect against peripheral salicylate ototoxicity in rats.
Sodium Salicylate (SS) reliably induces a sensorineural hearing loss and tinnitus when administered in high doses. Recent animal modeled studies indicate that potassium channel openers such as Maxipost and Retigabine (RTG) can block SS- or noise-induced tinnitus respectively; however, the origins and mechanisms are poorly understood. Since SS blocks the same potassium channels that Maxipost and RTG open, we postulated that these drugs might influence peripheral auditory function. To test this hypothesis Maxipost or RTG were administered alone or in combination with SS in rats. When administered alone, Maxipost and RTG had no effect on distortion product otoacoustic emissions (DPOAE) or compound action potentials (CAPs). However when Maxipost or RTG were administered with SS, Maxipost prevented the SS-reduced CAP amplitudes at high frequencies (≥20 kHz) and RTG prevented SS-reduced CAP amplitudes at low frequencies (≤8 kHz). These results suggest that Maxipost and RTG can protect against peripheral damage and therefore reduce the incidence of tinnitus.
Center for Hearing and Deafness, State University of New York at Buffalo, 137 Cary Hall, 3435 Main Street, Buffalo, NY 14214, USA. Electronic address: asheppar@buffalo.edu.
Adam M
AM
Sheppard
Center for Hearing and Deafness, State University of New York at Buffalo, 137 Cary Hall, 3435 Main Street, Buffalo, NY 14214, USA.
Guang-Di
GD
Chen
Center for Hearing and Deafness, State University of New York at Buffalo, 137 Cary Hall, 3435 Main Street, Buffalo, NY 14214, USA.
Richard
R
Salvi
D000161:Acoustic Stimulation; D000818:Animals; D002219:Carbamates / Q000494:pharmacology*; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism; D003055:Cochlear Microphonic Potentials / Q000187:drug effects; D019610:Cytoprotection; D004195:Disease Models, Animal; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007211:Indoles / Q000494:pharmacology*; D051656:KCNQ Potassium Channels / Q000819:agonists / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000819:agonists / Q000378:metabolism; D008297:Male; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects; D010655:Phenylenediamines / Q000494:pharmacology*; D015221:Potassium Channels / Q000819:agonists* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012980:Sodium Salicylate; D014012:Tinnitus / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*
C424388:BMS204352; D002219:Carbamates; D007211:Indoles; D051656:KCNQ Potassium Channels; C492166:Kcnq4 protein, rat; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010655:Phenylenediamines; D015221:Potassium Channels; C101866:ezogabine; D012980:Sodium Salicylate