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 GTPγS or GDPβS 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. © 1995 Wiley-Liss, Inc.