Activation of N-methyl- d-aspartate (NMDA) receptors augments repolarizing responses in lamprey spinal neurons

Abstract

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 Ca 2+ with Ba 2+. During voltage-clamp NM(DL)A enhanced a Ba 2+-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 oscillations observed under current-clamp. These results suggest that the repolarization during NMDA-induced oscillations is due to Ca 2+ entry both via NMDA-gated channels and conventional voltage-gated Ca 2+ channels, leading to an activation of Ca 2+-dependent K + channels. The afterhyperpolarization following single action potentials, which is also due to Ca 2+-dependent K + channels, was not significantly altered by NMDA receptor activation, suggesting a different location of the Ca 2+ entry during the two conditions in relation to the location of the activated Ca 2+-dependent K + channels.