Activation of NMDA receptors is required for the initiation and maintenance of walking-like activity in the mudpuppy (Necturus Maculatus).
We hypothesized that blocking the activation of N-methyl-D-aspartate (NMDA) receptors prevents the initiation of walking-like activity and abolishes the ongoing rhythmic activity in the spinal cord-forelimb preparation from the mudpuppy. Robust walking-like movements of the limb and rhythmic alternating elbow flexor-extensor EMG pattern characteristic of walking were elicited when continuous perfusion of the spinal cord with solution containing D-glutamate. The frequency of the walking-like activity was dose-dependent on the concentration of D-glutamate in the bath over a range of 0.2 to 0.9 mmol/L. Elevation of potassium concentrations failed to induce walking-like activity. Application of the selective antagonist 2-amino-5-phosphonovalerate (AP-5) produced dose-dependent block of the initiation and maintenance of walking-like activity induced by D-glutamate. Complete block of the activity was achieved when the concentration of AP-5 reached 20 micromol/L. Furthermore, application of L-701,324 (a selective antagonist of the strychnine-insensitive glycine site of NMDA receptor) (1-10 micromol/L) also resulted in complete block of the walking-like activity. In contrast, application of the non-NMDA receptor antagonist 6-cyno-7-nitroquinoxaline-2,3-dione (CNQX) (1-50 micromol/L) induced a dose-dependent inhibition of the burst frequency but failed to result in a complete block. Only at concentration as high as 100 micromol/L, did CNQX cause complete block of the rhythmic activity, presumably through nonspecific action on the strychnine-insensitive glycine site of NMDA receptors. These results suggest that activation of NMDA receptors is required for the initiation and maintenance of walking-like activity. Operation of non-NMDA receptors plays a powerful role in the modulation of the walking-like activity in the mudpuppy.
Lavrov
Igor
I
Neurophysiology Laboratory, Department of Anesthesiology, University of Louisville School of Medicine, 530 South Jackson Street, Louisville, KY 40202, USA.
Cheng
Jianguo
J
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D009338:Necturus maculosus / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D016138:Walking / Q000502:physiology*
D016194:Receptors, N-Methyl-D-Aspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione