Author:

Keywords:

Animals, Benzodiazepines, Calcium, Cell Culture Techniques, Electrophysiology, Immunohistochemistry, Ionophores, Monensin, Motor Neurons, Patch-Clamp Techniques, Potassium Channels, Voltage-Gated, Rats, Rats, Wistar, Receptors, AMPA, Research Support, Non-U.S. Gov't, Sodium, Spinal Cord, Science & Technology, Life Sciences & Biomedicine, Neurosciences, Physiology, Neurosciences & Neurology, OLIGODENDROCYTE PRECURSOR CELLS, GLUTAMATE RECEPTORS, OUTWARD CURRENTS, GLIAL-CELLS, KAINATE, CONDUCTANCE, ACTIVATION, EXPRESSION, NEURONS, 11 Medical and Health Sciences, 17 Psychology and Cognitive Sciences, Neurology & Neurosurgery, 32 Biomedical and clinical sciences, 42 Health sciences, 52 Psychology

Abstract:

alpha-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 Ca(2+) 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.