The effect of glutamate and inhibitors of NMDA receptors on postdenervation decrease of membrane potential in rat diaphragm
The early postdenervation depolarization of rat diaphragm muscle fibers (8–10 mV within 3 h in vitro) is substantially smaller (3 mV) when muscles are bathed with 1×10−3 M l-glutamate (Glu) or 1×10−3 M N-methyl-d-aspartate (NMDA). The effects of Glu and NMDA are inhibited in a dose-dependent manner by competitive inhibitor 2-amino-5-phosphonovaleric acid (APV) withK i 6.3×10−4 M, by 2×10−7 M MK-801, which acts as an open channel inhibitor, by 2–3×10−4 Zn2+, which reacts with surface-located sites of the NMDA subtype of the glutamate receptor, and also by glycine-free solutions and 7-Cl-kynurenic acid, which inhibits the glycine binding sites on NMDA receptors. It follows that the effect of glutamate on early postdenervation depolarization is mediated by the NMDA subtype of glutamate receptor with similar pharmacological properties to those found in neurons. The only exception found was the glutamate-like action of 1×10−7 M MK-801, which partially prevented the early postdenervation depolarization when present in the muscle bath during the first 3 h after nerve section.
Index EntriesGlutamate NMDA receptor APV MK-801 Zn2+ neuromuscular junction NO denervation
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