The Journal of Neurophysiology Vol. 88 No. 2 August 2002, pp. 965-972
Copyright ©2002 by the American Physiological Society

Na⁺ Entry Through AMPA Receptors Results in Voltage-Gated K⁺ Channel Blockade in Cultured Rat Spinal Cord Motoneurons

 ¹Laboratory for Neurobiology and  ²Laboratory for Physiology, Department of Neuroscience, University of Leuven, B-3000 Leuven, Belgium

Van Damme, P., L. Van den Bosch, E. Van Houtte, J. Eggermont, G. Callewaert, and W. Robberecht. Na⁺ Entry Through AMPA Receptors Results in Voltage-Gated K⁺ Channel Blockade in Cultured Rat Spinal Cord Motoneurons. J. Neurophysiol. 88: 965-972, 2002. -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 K_V and the transient outward K⁺ current, K_A. 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.