title: Thapsigargin suppresses cochlear potentials and DPOAEs and is toxic to hair cells.
abstract: Thapsigargin, a drug that inhibits sarco-endoplasmic reticulum Ca(2+) ATPases (SERCAs), was infused into the perilymph compartment of the guinea pig cochlea in increasing concentrations (0.1-10 microM) while sound evoked cochlear potentials were monitored. Thapsigargin significantly suppressed the compound action potential of the auditory nerve, cochlear microphonics, and increased N(1) latency at low (56 dB SPL) and high intensity (92 dB SPL) levels of sound, suppressed low intensity sound evoked summating potential (SP) and greatly increased the magnitude of the high intensity sound evoked SP. At 10 microM, the drug suppressed the cubic distortion product otoacoustic emissions (2f(1)-f(2)=8 kHz, f(2)=12 kHz) evoked by both high and low intensity primaries (45, 60, 70 dB SPL). Thapsigargin (10 microM; 30 min) increased the endocochlear potential slightly (5 mV). In chronic animals, thapsigargin (10 microM; 60 min) destroyed many outer hair cells and some inner hair cells, especially in the basal turns. These effects are consistent with the hypothesis that the inhibition of the SERCAs affects the function of the cochlear amplifier and outer hair cells to a greater degree than it affects other functions of the cochlea.
authors.affiliation: Kresge Hearing Research Laboratory, Department of Otorhinolaryngology and Biocommunication, Louisiana State University Health Sciences Center, 533 Bolivar Street, 5th Floor, New Orleans, LA 70112-2234, USA. rbobbi@lsuhsc.edu
authors.forename: Richard P
authors.initials: RP
authors.lastname: Bobbin
authors.forename: Margarett
authors.initials: M
authors.lastname: Parker
authors.forename: Luke
authors.initials: L
authors.lastname: Wall
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D003051:Cochlea / Q000187:drug effects / Q000473:pathology; D003055:Cochlear Microphonic Potentials / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000506:poisoning; D005260:Female; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects*; D018072:Hair Cells, Auditory, Outer / Q000473:pathology; D008297:Male; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects*; D010469:Perceptual Distortion; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019284:Thapsigargin / Q000494:pharmacology* / Q000506:poisoning
chemical_list: D004791:Enzyme Inhibitors; D019284:Thapsigargin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases