Effects of selected pharmacological agents on avian auditory and vestibular compound action potentials

Shunda R. Irons-Brown, Timothy A. Jones

Research output: Contribution to journalArticle

6 Citations (Scopus)

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-α-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 μM. The CNQX concentration effective in reducing auditory CAPs by 50% (EC 50) was approximately 20 μM. Glutamate (1 mM) as well as α-amino-3-hydroxy-5- methyl-4-isoxazole propionic acid (AMPA), a glutamate agonist, significantly reduced auditory CAPs (AMPA EC 50=100 μM). 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.

Original languageEnglish (US)
Pages (from-to)54-66
Number of pages13
JournalHearing Research
Volume195
Issue number1-2
DOIs
StatePublished - Sep 1 2004

Fingerprint

Action Potentials
Pharmacology
Dizocilpine Maleate
Glutamic Acid
Excitatory Amino Acid Antagonists
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Extracellular Fluid
Inner Ear
Kynurenic Acid
6-Cyano-7-nitroquinoxaline-2,3-dione
Isoxazoles
Excitatory Amino Acid Agonists
GABA-A Receptor Antagonists
Bicuculline
Kainic Acid
NG-Nitroarginine Methyl Ester
Glutamate Receptors
Gravitation
N-Methylaspartate
Carboxylic Acids

Keywords

  • A/D, analog-to digital
  • AC, alternating current
  • ADP, adenosine di-phosphate
  • AMPA
  • Balance
  • CNQX
  • Chicken
  • Cochlea
  • DAA
  • GABA
  • Glutamate
  • Gravity receptors
  • Hearing
  • Kainate
  • Kynurenate
  • L-NAME
  • MK-801
  • Maculae
  • NBQX
  • Post-synaptic receptors
  • Vestibular

ASJC Scopus subject areas

  • Sensory Systems

Cite this

Effects of selected pharmacological agents on avian auditory and vestibular compound action potentials. / Irons-Brown, Shunda R.; Jones, Timothy A.

In: Hearing Research, Vol. 195, No. 1-2, 01.09.2004, p. 54-66.

Research output: Contribution to journalArticle

@article{57e4a840ca034e7b94fdcdc37523a8cd,
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-α-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 μM. The CNQX concentration effective in reducing auditory CAPs by 50{\%} (EC 50) was approximately 20 μM. Glutamate (1 mM) as well as α-amino-3-hydroxy-5- methyl-4-isoxazole propionic acid (AMPA), a glutamate agonist, significantly reduced auditory CAPs (AMPA EC 50=100 μM). 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.",
keywords = "A/D, analog-to digital, AC, alternating current, ADP, adenosine di-phosphate, AMPA, Balance, CNQX, Chicken, Cochlea, DAA, GABA, Glutamate, Gravity receptors, Hearing, Kainate, Kynurenate, L-NAME, MK-801, Maculae, NBQX, Post-synaptic receptors, Vestibular",
author = "Irons-Brown, {Shunda R.} and Jones, {Timothy A.}",
year = "2004",
month = "9",
day = "1",
doi = "10.1016/j.heares.2004.02.011",
language = "English (US)",
volume = "195",
pages = "54--66",
journal = "Hearing Research",
issn = "0378-5955",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Effects of selected pharmacological agents on avian auditory and vestibular compound action potentials

AU - Irons-Brown, Shunda R.

AU - Jones, Timothy A.

PY - 2004/9/1

Y1 - 2004/9/1

N2 - 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-α-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 μM. The CNQX concentration effective in reducing auditory CAPs by 50% (EC 50) was approximately 20 μM. Glutamate (1 mM) as well as α-amino-3-hydroxy-5- methyl-4-isoxazole propionic acid (AMPA), a glutamate agonist, significantly reduced auditory CAPs (AMPA EC 50=100 μM). 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.

AB - 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-α-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 μM. The CNQX concentration effective in reducing auditory CAPs by 50% (EC 50) was approximately 20 μM. Glutamate (1 mM) as well as α-amino-3-hydroxy-5- methyl-4-isoxazole propionic acid (AMPA), a glutamate agonist, significantly reduced auditory CAPs (AMPA EC 50=100 μM). 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.

KW - A/D, analog-to digital

KW - AC, alternating current

KW - ADP, adenosine di-phosphate

KW - AMPA

KW - Balance

KW - CNQX

KW - Chicken

KW - Cochlea

KW - DAA

KW - GABA

KW - Glutamate

KW - Gravity receptors

KW - Hearing

KW - Kainate

KW - Kynurenate

KW - L-NAME

KW - MK-801

KW - Maculae

KW - NBQX

KW - Post-synaptic receptors

KW - Vestibular

UR - http://www.scopus.com/inward/record.url?scp=4444321692&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4444321692&partnerID=8YFLogxK

U2 - 10.1016/j.heares.2004.02.011

DO - 10.1016/j.heares.2004.02.011

M3 - Article

C2 - 15350279

AN - SCOPUS:4444321692

VL - 195

SP - 54

EP - 66

JO - Hearing Research

JF - Hearing Research

SN - 0378-5955

IS - 1-2

ER -