Borges K, Kettenmann H
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia, USA.
J Neurosci Res. 1995 Nov 1;42(4):579-93. doi: 10.1002/jnr.490420416.
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.
胚胎小鼠皮质培养的少突胶质前体细胞中AMPA/海人藻酸受体激活导致延迟整流钾电流的阻断。在本研究中，我们采用全细胞膜片钳技术提供证据表明，海人藻酸受体激活与钾电导阻断之间的机制是由于受体介导的钠离子内流：1）在无钠的浴液中未观察到阻断现象，当用含高浓度钠离子的移液管溶液透析细胞使细胞内[钠离子]升高时也未观察到阻断现象。2）与用蔗糖透析的细胞相比，单独升高细胞内[钠离子]会导致外向电流的阻断。高浓度的[锂离子]i也会降低外向电流，并且在含锂的浴液中，海人藻酸诱导的钾通道阻断更为明显。可能是由于排出机制较慢，锂离子在通过受体孔渗透后在细胞内积累。用GTPγS或GDPβS以及百日咳毒素进行的实验表明，GTP结合蛋白介导的机制对海人藻酸诱导的钾电导阻断并不重要。我们的数据表明，在胶质前体细胞中，AMPA/海人藻酸受体激活导致细胞内[钠离子]增加，从而阻断延迟整流钾通道。
