Activation of N-methyl-D-aspartate (NMDA) receptors augments repolarizing responses in lamprey spinal neurons.
Current- and voltage-clamp techniques were used to analyze the mechanisms underlying the repolarization during N-methyl-D-aspartate (NMDA)-induced, tetrodotoxin-resistant pacemaker-like oscillations in lamprey spinal neurons. Long-lasting depolarizing current pulses (15-40 mV, 50-400 ms, tetrodotoxin and tetraethylammonium present) were followed by hyperpolarizing afterpotentials even when NMDA receptors were blocked, but they were markedly enhanced by application of N-methyl-D,L-aspartate (NM(DL)A). The afterpotentials were depressed by replacing Ca2+ with Ba2+. During voltage-clamp NM(DL)A enhanced a Ba2+-sensitive outward tail current following voltage steps of 15-40 mV. The outward current remained after injection of Cl-, as did the NMDA-induced membrane potential oscillations observed under current-clamp. These results suggest that the repolarization during NMDA-induced oscillations is due to Ca2+ entry both via NMDA-gated channels and conventional voltage-gated Ca2+ channels, leading to an activation of Ca2+-dependent K+ channels. The afterhyperpolarization following single action potentials, which is also due to Ca2+-dependent K+ channels, was not significantly altered by NMDA receptor activation, suggesting a different location of the Ca2+ entry during the two conditions in relation to the location of the activated Ca2+-dependent K+ channels.
Hill
R H
RH
Nobel Institute for Neurophysiology, Karolinska Institutet, Stockholm, Sweden.
Brodin
L
L
Grillner
S
S
D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D005399:Fishes / Q000502:physiology*; D066298:In Vitro Techniques; D007798:Lampreys / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D016202:N-Methylaspartate