Na(+) entry through AMPA receptors results in voltage-gated k(+) channel blockade in cultured rat spinal cord motoneurons.
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.
Van Damme
P
P
Laboratory for Neurobiology, Department of Neuroscience, University of Leuven, Belgium. philip.vandamme@med.kuleuven.ac.be
Van Den Bosch
L
L
Van Houtte
E
E
Eggermont
J
J
Callewaert
G
G
Robberecht
W
W
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D018929:Cell Culture Techniques; D004594:Electrophysiology; D007150:Immunohistochemistry; D007476:Ionophores / Q000494:pharmacology; D008985:Monensin / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D007476:Ionophores; D024642:Potassium Channels, Voltage-Gated; D018091:Receptors, AMPA; D001569:Benzodiazepines; D008985:Monensin; D012964:Sodium; C085266:talampanel; D002118:Calcium