title: Effects of selected pharmacological agents on avian auditory and vestibular compound action potentials.
abstract: Glutamate is currently the consensus candidate for the hair cell transmitter in the inner ear of vertebrates. However, other candidate transmitter systems have been proposed and there may be differences in this regard for auditory and vestibular neuroepithelia. In the present study, perilymphatic perfusion was used to deliver prescribed concentrations of ten drugs to the interstitial fluids of the inner ear of hatchling chickens (n = 124). Dose-response curves were obtained for four of these pharmacological agents. The work was carried out in part to distinguish further the neuroepithelial chemical receptors mediating auditory and vestibular compound action potentials (CAPs). Kainic acid (KA) eliminated both auditory and vestibular responses. D-alpha-Aminoadipic acid (DAA) and dizocilpine maleate (MK-801), both NMDA-specific antagonists, failed to alter vestibular CAPs at any concentration. MK-801 significantly and selectively reduced auditory CAPs at concentrations equal to or greater than 1 mM. Similarly, kynurenic acid (4-hydroxyquinoline-2-carboxylic acid, 1 mM), a glutamate antagonist, significantly reduced auditory but not vestibular CAPs. A non-NMDA glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), reduced vestibular CAPs significantly but only at the highest concentration tested (1 mM). In contrast, CNQX reduced auditory responses at concentration as low as 1 microM. The CNQX concentration effective in reducing auditory CAPs by 50% (EC(50)) was approximately 20 microM. Glutamate (1 mM) as well as alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), a glutamate agonist, significantly reduced auditory CAPs (AMPA EC(50)=100 microM). Bicuculline, a GABA(A) receptor antagonist, and L-NAME, a nitric oxide synthase inhibitor, failed to alter responses from either modality. These findings support the hypothesis that glutamate receptors mediate auditory CAPs in birds. However, the results underscore a remarkable difference in sensitivity of the vestibular neuroepithelium (here gravity receptors) to non-NMDA receptor antagonists. The basis of the vestibular insensitivity to glutamate blockers is unknown but it may reflect differences in receptors themselves, differences in the transmission modes available to vestibular synapses or differences in the access of compounds to vestibular neuroepithelial receptors from the interstitial-perilymphatic fluid spaces.
authors.affiliation: Department of Medical Pharmacology and Physiology, University of Missouri-Columbia, Columbia, MO 65212, USA.
authors.forename: Shunda R
authors.initials: SR
authors.lastname: Irons-Brown
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Jones
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D002645:Chickens / Q000502:physiology*; D003056:Cochlear Nerve / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D014725:Vestibular Nerve / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester