Channelpedia

PubMed 16925593


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kir1.1 , Kir4.1



Title: Progressive loss of a glial potassium channel (KCNJ10) in the spinal cord of the SOD1 (G93A) transgenic mouse model of amyotrophic lateral sclerosis.

Authors: Melanie Kaiser, Iris Maletzki, Swen Hülsmann, Bettina Holtmann, Walter Schulz-Schaeffer, Frank Kirchhoff, Mathias Bähr, Clemens Neusch

Journal, date & volume: J. Neurochem., 2006 Nov , 99, 900-12

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16925593


Abstract
Transgenic mice expressing the superoxide dismutase G93A mutation (SOD1(G93A)) were used to investigate the role of glial inwardly rectifying K(+) (Kir)4.1 channels, which buffer extracellular K(+) increases in response to neuronal excitation. A progressive decrease in Kir4.1 immunoreactivity was observed predominantly in the ventral horn of SOD1(G93A) mutants. Immunoblotting of spinal cord extracts mirrored these changes by showing a loss of Kir4.1 channels from presymptomatic stages onwards. Kir4.1 channels were found to be expressed in the spinal cord grey matter, targetting astrocytes and clustering around capillaries, supporting their role in clearance of extracellular K(+). To understand the functional implications of extracellular K(+) increases, we challenged the NSC34 motor neurone cell line with increasing extracellular K(+) concentrations. Exposure to high extracellular K(+) induced progressive motor neurone cell death. We suggest that loss of Kir4.1 impairs perineural K(+) homeostasis and may contribute to motor neurone degeneration in SOD1(G93A) mutants by K(+) excitotoxic mechanisms.