Ouabain application to the round window of the gerbil cochlea: a model of auditory neuropathy and apoptosis.
The physiological and morphological changes resulting from acute and chronic infusion of ouabain onto the intact round-window (RW) membrane were examined in the gerbil cochlea. Osmotic pumps fitted with cannulas allowed chronic (0.5-8 days) infusions of ouabain. Acute and short-term applications of ouabain (1-24 h) induced an increase in auditory-nerve compound action potential (CAP) thresholds at high frequencies with lower frequencies unaffected. The resulting threshold shifts were basically all (no response) or none (normal thresholds), with a sharp demarcation between high and low frequencies. Survival times of 2 days or greater after ouabain exposure resulted in complete auditory neuropathy with no CAP response present at any frequency. Distortion product otoacoustic emissions (DPOAEs) and the endocochlear potential (EP) were largely unaffected by the ouabain indicating normal function of the outer hair cells (OHC) and stria vascularis. One to 3 days after short-term applications, apoptosis was evident among the spiral ganglion neurons assessed both morphologically and with TdT-mediated dUTP-biotin nick end labeling (TUNEL). With 4-8 day survival times, most spiral ganglion cells were absent; however, a few cell bodies remained intact in many ganglia profiles. These surviving neurons had many of the characteristics of type II afferents. Our working hypothesis is that the ouabain induces a spreading depression among the type I ganglion cells by blocking the Na,K-ATPase pump. Because of the constant spike activity of these cells, the ouabain rapidly alters potassium concentrations within ([K+]i) and external to ([K+]o) the ganglion cells, thereby initiating an apoptotic cascade.
Schmiedt
R A
RA
Department of Otolaryngology and Head-Neck Surgery, Medical University of South Carolina, Charleston, SC 29425, USA. schmiera@musc.edu
Okamura
H-O
HO
Lang
H
H
Schulte
B A
BA
D000200:Action Potentials; D000818:Animals; D017209:Apoptosis; D003051:Cochlea / Q000503:physiopathology; D003056:Cochlear Nerve / Q000503:physiopathology*; D004056:Differential Threshold; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D005849:Gerbillinae; D008959:Models, Neurological; D017084:Otoacoustic Emissions, Spontaneous; D010042:Ouabain / Q000008:administration & dosage* / Q000494:pharmacology; D010469:Perceptual Distortion; D012405:Round Window, Ear / Q000187:drug effects*; D000160:Vestibulocochlear Nerve Diseases / Q000139:chemically induced*
D004791:Enzyme Inhibitors; D010042:Ouabain