Blockade of K+ channels induced by AMPA/kainate receptor activation in mouse oligodendrocyte precursor cells is mediated by Na+ entry.
AMPA/kainate receptor activation in cultured oligodendrocyte precursor cells from embryonic mouse cortex leads to a blockade of delayed rectifying K+ currents. In the present study, we provide evidence using the patch-clamp technique in the whole-cell configuration that the mechanism linking kainate receptor activation and K+ conductance blockade is due to the receptor-mediated Na+ entry: 1) The blockade was not observed in Na(+)-free bathing solution nor when intracellular [Na+] was elevated by dialzying the cell with a pipette solution containing high [Na+]. 2) Elevation of intracellular [Na+] alone led to a blockade of outward currents in contrast to cells dialyzed by sucrose. High [Li+]i also reduced the outward currents, and in Li(+)-containing bathing solution the kainate-induced blockade of K+ channels was more pronounced. Probably, Li+ accumulates intracellularly after permeation through the receptor pore due to slower extrusion mechanisms. Experiments with GTP gamma S or GDP beta S and pertussis toxin indicated that GTP-binding protein-mediated mechanisms were not of importance for the kainate-induced K+ conductance blockade. Our data suggest that in glial precursor cells AMPA/kainate receptor activation leads to an intracellular [Na+] increase which blocks delayed rectifying K+ channels.
Borges
K
K
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia, USA.
Kettenmann
H
H
D000818:Animals; D002478:Cells, Cultured / Q000502:physiology / Q000648:ultrastructure; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000502:physiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009836:Oligodendroglia / Q000502:physiology / Q000648:ultrastructure*; D037342:Pertussis Toxin; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D026902:Potassium Channel Blockers; D018091:Receptors, AMPA / Q000819:agonists*; D018092:Kainic Acid Receptors / Q000819:agonists*; D012964:Sodium / Q000378:metabolism* / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D019204:GTP-Binding Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006153:Guanosine Diphosphate; D037342:Pertussis Toxin; D011188:Potassium; D026902:Potassium Channel Blockers; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; C023427:guanosine 5'-O-(2-thiodiphosphate)