Na+ Entry Through AMPA Receptors Results in Voltage-Gated K+ Channel Blockade in Cultured Rat Spinal Cord Motoneurons
α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor currents, evoked with the agonist kainate, were studied with the gramicidin perforated-patch-clamp technique in cultured rat spinal cord motoneurons. Kainate-induced currents could be blocked by the AMPA receptor antagonist LY 300164 and displayed an apparent strong inward rectification. This inward rectification was not a genuine property of AMPA receptor currents but was a result of a concomitant decrease in outward current at potentials positive to −40.5 ± 1.3 mV. The AMPA receptor current itself was nearly linear (rectification index 0.91). The kainate-inhibited outward current had a reversal potential close to the estimated K+equilibrium potential and was blocked by 30 mM tetraethylammonium. When voltage steps were applied, it was found that kainate inhibited both the delayed rectifier K+ current KV and the transient outward K+ current, KA. The kainate-induced inhibition of K+ currents was dependent on ion flux through the AMPA receptor, because no change in the membrane conductance was noticed in the presence of LY 300164. Removing extracellular Ca2+ had no effect, whereas replacing extracellular Na+ or clamping the membrane close to the estimated Na+equilibrium potential during kainate application attenuated the inhibition of the K+ current. Sustained Na+ influx induced by application of the Na+ ionophore monensin could mimic the effect of kainate on K+ conductance. These findings demonstrate that Na+ influx through AMPA receptors results in blockade of voltage-gated K+channels.