Time-varying alterations in the f2-f1 DPOAE response to continuous primary stimulation. II. Influence of local calcium-dependent mechanisms.
The distortion product otoacoustic emission (DPOAE) corresponding to the frequency f2-f1 displays stereotyped, time-varying amplitude alterations during continuous primary tone stimulation. The origin of these alterations is unknown; however, evidence that efferent neurons contribute little to the changes has been presented (Kujawa et al., 1994a, 1995; Lowe and Robertson, 1995). The present investigation examines the hypothesis that these alterations in f2-f1 amplitude are a reflection of local, Ca(2+)-dependent mechanisms involving the outer hair cell (OHC) response to sustained stimulation. Experiments were performed using urethane-anesthetized guinea pigs with sectioned middle ear muscles. Intracochlear perfusion was employed to reversibly lower perilymph Ca2+ levels and to introduce antagonists and agonists of L-type Ca2+ channels. Manipulations that lowered available Ca2+ (zero Ca2+ artificial perilymph; zero Ca2+ with BAPTA) or that blocked its entry into the cell via L-type Ca2+ channels (nimodipine) reduced, prevented or reversed the perstimulatory changes in f2-f1 DPOAE amplitude. These perilymph manipulations also reduced the overall amplitude of this distortion component while perfusion of an L-type Ca2+ channel agonist (Bay K 8644) increased its amplitude. Mg2+ did not substitute for Ca2+, suggesting that these are not merely divalent cation effects. Results are consistent with the hypothesis that continuous stimulation-related changes in f2-f1 DPOAE amplitude are sensitive to perilymph Ca2+ levels and to the function of L-type Ca2+ channels. However, nimodipine also reduced the endocochlear potential (EP) and Bay K 8644 increased the EP. The sensitivity of both the perstimulatory changes in f2-f1 DPOAE amplitude and the EP to the latter drugs leaves their site(s) of action unresolved.
Kujawa
S G
SG
Kresge Hearing Research Laboratory, Department of Otorhinolaryngology and Biocommunication, Louisiana State University Medical Center, New Orleans 70112, USA.
Fallon
M
M
Skellett
R A
RA
Bobbin
R P
RP
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000161:Acoustic Stimulation; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D003055:Cochlear Microphonic Potentials / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000166:cytology / Q000187:drug effects*; D008274:Magnesium / Q000378:metabolism; D008297:Male; D009553:Nimodipine / Q000494:pharmacology; D017084:Otoacoustic Emissions, Spontaneous; D010498:Perilymph / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D002121:Calcium Channel Blockers; D002614:Chelating Agents; D004533:Egtazic Acid; D009553:Nimodipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D008274:Magnesium; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D004121:Dimethyl Sulfoxide