Deafness disrupts chloride transporter function and inhibitory synaptic transmission.
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 E(IPSC) 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.
Vale
Carmen
C
School of Medicine and Centro Regional de Investigaciones Biomedicas, University of Castilla-La Mancha, Albacete 02071, Spain.
Schoorlemmer
Jon
J
Sanes
Dan H
DH
D000818:Animals; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D003638:Deafness / Q000378:metabolism* / Q000503:physiopathology*; D005071:Evoked Potentials; D019706:Excitatory Postsynaptic Potentials; D005849:Gerbillinae; D007245:Inferior Colliculi / Q000502:physiology; D017136:Ion Transport; D009433:Neural Inhibition; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D011188:Potassium / Q000494:pharmacology; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism / Q000502:physiology*; D064506:Solute Carrier Family 12, Member 2; D027981:Symporters / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission; D000096922:K Cl- Cotransporters
D002712:Chlorides; D011188:Potassium; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D027981:Symporters; D000096922:K Cl- Cotransporters