Deafness disrupts chloride transporter function and inhibitory synaptic transmission

Carmen Vale, Jon Schoorlemmer, Dan Sanes

Research output: Contribution to journalArticle

Abstract

Loss of sensory function leads to atrophy or death within the developing CNS, yet little is known about the physiology of remaining synapses. After bilateral deafening, gramicidin-perforated-patch recordings were obtained from gerbil inferior colliculus neurons in a brain slice preparation. Afferent-evoked IPSPs had a diminished ability to block current-evoked action potentials in deafened neurons. This change could be attributed, in part, to a loss of potassium-dependent chloride transport function, with little change in K-Cl cotransporter expression. Treatments that suppressed chloride cotransport (bumetanide, cesium, and genistein) had little or no effect on neurons from deafened animals. These same treatments depolarized the E1PSC of control neurons. Semiquantitative RT-PCR and immunohistochemical staining indicated no change in the expression of chloride cotransporter mRNA or protein after deafness. Therefore, profound hearing loss leads rapidly to the disruption of chloride homeostasis, which is likely attributable to the dysfunction of the potassium-dependent chloride cotransport mechanism, rather than a downregulation of its expression. This results in inhibitory synapses that are less able to block excitatory events.

Original languageEnglish (US)
Pages (from-to)7516-7524
Number of pages9
JournalJournal of Neuroscience
Volume23
Issue number20
StatePublished - Aug 20 2003

Fingerprint

Deafness
Synaptic Transmission
Chlorides
Neurons
Potassium Chloride
Synapses
Bumetanide
Gramicidin
Inferior Colliculi
Inhibitory Postsynaptic Potentials
Cesium
Aptitude
Gerbillinae
Genistein
Hearing Loss
Evoked Potentials
Action Potentials
Atrophy
Homeostasis
Down-Regulation

Keywords

  • Auditory
  • Development
  • Gerbil
  • Inferior colliculus
  • Inhibition
  • KCC2
  • Plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Deafness disrupts chloride transporter function and inhibitory synaptic transmission. / Vale, Carmen; Schoorlemmer, Jon; Sanes, Dan.

In: Journal of Neuroscience, Vol. 23, No. 20, 20.08.2003, p. 7516-7524.

Research output: Contribution to journalArticle

Vale, Carmen ; Schoorlemmer, Jon ; Sanes, Dan. / Deafness disrupts chloride transporter function and inhibitory synaptic transmission. In: Journal of Neuroscience. 2003 ; Vol. 23, No. 20. pp. 7516-7524.
@article{19cd5c39a1e545e0bbc50ebcb0cc8f79,
title = "Deafness disrupts chloride transporter function and inhibitory synaptic transmission",
abstract = "Loss of sensory function leads to atrophy or death within the developing CNS, yet little is known about the physiology of remaining synapses. After bilateral deafening, gramicidin-perforated-patch recordings were obtained from gerbil inferior colliculus neurons in a brain slice preparation. Afferent-evoked IPSPs had a diminished ability to block current-evoked action potentials in deafened neurons. This change could be attributed, in part, to a loss of potassium-dependent chloride transport function, with little change in K-Cl cotransporter expression. Treatments that suppressed chloride cotransport (bumetanide, cesium, and genistein) had little or no effect on neurons from deafened animals. These same treatments depolarized the E1PSC of control neurons. Semiquantitative RT-PCR and immunohistochemical staining indicated no change in the expression of chloride cotransporter mRNA or protein after deafness. Therefore, profound hearing loss leads rapidly to the disruption of chloride homeostasis, which is likely attributable to the dysfunction of the potassium-dependent chloride cotransport mechanism, rather than a downregulation of its expression. This results in inhibitory synapses that are less able to block excitatory events.",
keywords = "Auditory, Development, Gerbil, Inferior colliculus, Inhibition, KCC2, Plasticity",
author = "Carmen Vale and Jon Schoorlemmer and Dan Sanes",
year = "2003",
month = "8",
day = "20",
language = "English (US)",
volume = "23",
pages = "7516--7524",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "20",

}

TY - JOUR

T1 - Deafness disrupts chloride transporter function and inhibitory synaptic transmission

AU - Vale, Carmen

AU - Schoorlemmer, Jon

AU - Sanes, Dan

PY - 2003/8/20

Y1 - 2003/8/20

N2 - Loss of sensory function leads to atrophy or death within the developing CNS, yet little is known about the physiology of remaining synapses. After bilateral deafening, gramicidin-perforated-patch recordings were obtained from gerbil inferior colliculus neurons in a brain slice preparation. Afferent-evoked IPSPs had a diminished ability to block current-evoked action potentials in deafened neurons. This change could be attributed, in part, to a loss of potassium-dependent chloride transport function, with little change in K-Cl cotransporter expression. Treatments that suppressed chloride cotransport (bumetanide, cesium, and genistein) had little or no effect on neurons from deafened animals. These same treatments depolarized the E1PSC of control neurons. Semiquantitative RT-PCR and immunohistochemical staining indicated no change in the expression of chloride cotransporter mRNA or protein after deafness. Therefore, profound hearing loss leads rapidly to the disruption of chloride homeostasis, which is likely attributable to the dysfunction of the potassium-dependent chloride cotransport mechanism, rather than a downregulation of its expression. This results in inhibitory synapses that are less able to block excitatory events.

AB - Loss of sensory function leads to atrophy or death within the developing CNS, yet little is known about the physiology of remaining synapses. After bilateral deafening, gramicidin-perforated-patch recordings were obtained from gerbil inferior colliculus neurons in a brain slice preparation. Afferent-evoked IPSPs had a diminished ability to block current-evoked action potentials in deafened neurons. This change could be attributed, in part, to a loss of potassium-dependent chloride transport function, with little change in K-Cl cotransporter expression. Treatments that suppressed chloride cotransport (bumetanide, cesium, and genistein) had little or no effect on neurons from deafened animals. These same treatments depolarized the E1PSC of control neurons. Semiquantitative RT-PCR and immunohistochemical staining indicated no change in the expression of chloride cotransporter mRNA or protein after deafness. Therefore, profound hearing loss leads rapidly to the disruption of chloride homeostasis, which is likely attributable to the dysfunction of the potassium-dependent chloride cotransport mechanism, rather than a downregulation of its expression. This results in inhibitory synapses that are less able to block excitatory events.

KW - Auditory

KW - Development

KW - Gerbil

KW - Inferior colliculus

KW - Inhibition

KW - KCC2

KW - Plasticity

UR - http://www.scopus.com/inward/record.url?scp=0041419771&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0041419771&partnerID=8YFLogxK

M3 - Article

C2 - 12930790

AN - SCOPUS:0041419771

VL - 23

SP - 7516

EP - 7524

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 20

ER -