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 x 10(-3) M L-glutamate (Glu) or 1 x 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) with Ki 6.3 x 10(-4) M, by 2 x 10(-7) M MK-801, which acts as an open channel inhibitor, by 2-3 x 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.

Acetylcholine and carbachol prevent muscle depolarization in denervated rat diaphragm.

Muscle fibres of the rat diaphragm kept in a tissue culture medium became depolarized by 8-10 mV within 3 h after denervation. In the presence of carbachol (CB; 5 x 10(-8) M), and acetylcholine (ACh; 5 x 10(-8) M, the post-denervation depolarization was reduced. Both drugs were used in concentrations which mimicked the effect of non-quantal release of ACh.

Nitroprusside decreases the early post-denervation depolarization of diaphragm muscle fibres of the rat.

The application of sodium nitroprusside, which degrades to nitric oxide (NO) in solution, inhibits early post-denervation depolarization of isolated rat diaphragm fibres. The observation that "old' solutions of sodium nitroprusside (that have been allowed to decompose) are without effect and that haemoglobin, oxadiazolo quinoxalinone (ODQ) and methylene blue can antagonize the inhibition normally produced by sodium nitroprusside suggests that the inhibitory effects of sodium nitroprusside on early post-denervation depolarization are mediated by NO and guanylyl cyclase. This is in accord with our recent observations with NO synthase activation and inhibition in the diaphragm.

Muscle NMDA receptors regulate the resting membrane potential through NO-synthase.

The early postdenervation depolarization of rat diaphragm muscle fibres (8-10 mV) is substantially smaller (3 mV) when muscle strips are bathed with 1 mM L-glutamate (GLU) or N-methyl-D-aspartate (NMDA). The effects of GLU and NMDA are not seen in the presence of aminophosphonovaleric acid (APV), a blocker of NMDA-subtype of glutamate receptors, 5 mM Mg2+ (which blocks NMDA-controlled ion channels) and L-nitroarginine methylester (NAME), an inhibitor of NO-synthase. This indicates that NMDA-subtype of GLU receptors might be involved in the regulation of the membrane potential in muscle fibres, most probably through the NO-synthase system.