Disruption of KCC2 reveals an essential role of K-Cl cotransport already in early synaptic inhibition.
By C. Hübner, V. Stein, I. Hermans-Borgmeyer, T. Meyer, K. Ballanyi, T. Jentsch. Neuron, 2001
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Synaptic inhibition by GABA(A) and glycine receptors, which are ligand-gated anion channels, depends on the electrochemical potential for chloride. Several potassium-chloride cotransporters can lower the intracellular chloride concentration [Cl(-)](i), including the neuronal isoform KCC2. We show that KCC2 knockout mice died immediately after birth due to severe motor deficits that also abolished respiration. Sciatic nerve recordings revealed abnormal spontaneous electrical activity and altered spinal cord responses to peripheral electrical stimuli. In the spinal cord of wild-type animals, the KCC2 protein was found at inhibitory synapses. Patch-clamp measurements of embryonic day 18.5 spinal cord motoneurons demonstrated an excitatory GABA and glycine action in the absence, but not in the presence, of KCC2, revealing a crucial role of KCC2 for synaptic inhibition.
Subfields: Cellular and Molecular Neuroscience, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/43e0bfb9de193824161dffeffb631d47565f7e4a
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Citations in the corpus
- Molecular physiology and pathophysiology of electroneutral cation-chloride cotransporters. (2005, background): “4) Impaired functional properties Bartter syndrome-BSC1 (384) Anderman syndrome-KCC3 (184) 5 1”
- Raising cytosolic Cl− in cerebellar granule cells affects their excitability and vestibulo‐ocular learning (2012, positive): “The neuronal expression of Nkcc1 generally decreases postnatally (Hu¨bner et al , 2001a; Mikawa et al , 2002), but cerebellar GCs retain substantial Nkcc1 expression throughout adult-hood (Kanaka et al , 2001; Hu¨bner et al , 2001a; Mikawa et al , 2002).”