Adenosine triphosphoric acid as a factor of nervous regulation of Na+/K+/2Cl- cotransport in rat skeletal muscle fibers.

Exogenous adenosine triphosphoric acid produces a biphasic effect on the resting membrane potential of muscle fibers in rat diaphragm. Depolarization of the sarcolemma observed 10 min after application of adenosine triphosphoric acid results from activation of Na(+)/K(+)/2Cl(-) cotransport. The increase in chloride cotransport is related to activation of postsynaptic P2Y receptors and protein kinase C. Repolarization of the membrane develops 40 min after treatment with adenosine triphosphoric acid and after 50 min the resting membrane potential almost returns the control level. This increase in the resting membrane potential of the sarcolemma is probably associated with activation of the Na(+)/K(+) pump and increase in membrane permeability for chlorine ions in response to long-term activity of Cl(-) cotransport. Thus, adenosine triphosphoric acid co-secreted with acetylcholine in the neuromuscular synapse probably plays a role in the regulation resting membrane potential and cell volume of muscle fibers.

Effect of dipeptide N-acetylaspartylglutamate on denervation-induced changes in the volume of rat skeletal muscle fibers.

N-acetylaspartylglutamate prevents the denervation-induced increase in the volume of muscle fibers in rat diaphragm, the phenomenon being more pronounced for the hydrolysable isomer. The effect of dipeptide manifested against the background of blockade of metabotropic glutamate receptors. It was hypothesized that N-acetylaspartylglutamate is involved in the regulation of the volume of skeletal muscle fibers via activation of ionotropic receptors by both dipeptide and glutamate molecules.

[Glutamatergic modulation of vertebrate neuromuscular transmission]. / Gluitamatérgicheskaia moduliatsiia nervno-myshechnoi peredachi u pozvonochnykh.

The paper is devoted to the analysis of evidence pointing to presence of glutamatergic modulation of vertebrate neuromuscular transmission. The data on the glutamate's origin and release in the endplate region as well as on the presence of specific glutamate receptors are discussed. The effects of glutamate on different types of acetylcholine secretion in the synapses of amphibians and mammals are described. The question of possible physiological role of glutamatergic modulation of neuromuscular transmission is discussed.

Effect of oxotremorine on resting membrane potential and cell volume in skeletal muscle fibers in rats after in vivo blockade of NO-synthase.

Denervation of rat phrenic muscle or block of NO-synthase in vivo increased the cross-section area of muscle fibers and decreased membrane resting potential. Oxotremorine prevented the development of denervation-induced or denervation-like (i.e. induced by NO-synthase blockade) membrane depolarization and increase of the cross-sectional area of muscle fibers. Pirenzepine abolished the effects of oxotremorine. It was concluded that non-quantal acetylcholine can be involved in the regulation of skeletal muscle fiber volume via activation of M1 muscarinic receptors followed by NO synthesis.

The effects of glutamate on spontaneous acetylcholine secretion processes in the rat neuromuscular synapse.

Experiments on rat diaphragm muscles showed that glutamate (10 microM-1 mM) had no effect on the mean frequency, interspike intervals, and amplitude-time characteristics of miniature endplate potentials, but had a suppressive action on non-quantum secretion (the intensity of which was assessed in terms of the H effect). The effect of glutamate was markedly concentration-dependent and was completely overcome by blockade of NMDA receptors, inhibition of NO synthase, and by binding of NO molecules in the extracellular space by hemoglobin. It is suggested that glutamate can modulate the non-quantum release of acetylcholine, initiating the synthesis of NO molecules in muscle fibers via activation of NMDA receptors followed by the retrograde action of NO on nerve terminals.

Glutamine uptake and metabolism to N-acetylaspartylglutamate (NAAG) by crayfish axons and glia.

We have proposed that N-acetylaspartylglutamate (NAAG) or its hydrolytic product glutamate, is a chemical signaling agent between axons and periaxonal glia at non-synaptic sites in crayfish nerves, and that glutamine is a probable precursor for replenishing the releasable pool of NAAG. We report here, that crayfish central nerve fibers synthesize NAAG from exogenous glutamine. Cellular accumulation of radiolabel during in vitro incubation of desheathed cephalothoracic nerve bundles with [3H]glutamine was 74% Na(+)-independent. The Na(+)-independent transport was temperature-sensitive, linear with time for at least 4 h, saturable between 2.5 and 10 mM L-glutamine, and blocked by neutral amino acids and analogs that inhibit mammalian glutamine transport. Radiolabeled glutamine was taken up and metabolized by both axons and glia to glutamate and NAAG, and a significant fraction of these products effluxed from the cells. Both the metabolism and release of radiolabeled glutamine was influenced by extracellular Na(+). The uptake and conversion of glutamine to glutamate and NAAG by axons provides a possible mechanism for recycling and formation of the axon-to-glia signaling agent(s).

[Pharmacological parameters of muscarinic cholinoreceptors in skeletal muscles]. / Farmakologicheskie osobennosti muskarinovykh cholinoretseptorov skeletnykh myshts.

It has been shown that bath application of muscarine delayed the early post-denervation depolarization in the muscle fibers incubated for 3 h in culture medium. The greatest reduction of the post-devervation depolarization was observed with 50 nmol/l muscarine. Atropine, a muscarinic antagonist, clozapine, a specific inhibitor of M1/M5-cholinergic receptors, and nitrocaramiphen, a M1-antagonist, completely removed the hyperpolarizing effect of muscarine. 4-DAMP, a specific inhibitor of M3-cholinergic receptors, himbacine, an antagonist of M2-cholinergic receptors, and tropicamide, a specific inhibitor of M2/M4-cholinergic receptors, failed to prevent the effect of muscarine. A M1/M2 muscarine agonists propargyl and but-2-ynyl esters of arecaidine had apparent muscarine-like effect. Nitrocaramiphen, and not himbacine, prevented the hyperpolarizing effect of these cholinomimetics. It is concluded that muscarine and esters of arecaidine delay the development of early postdenervation depolarization in M1-cholinergic receptors of skeletal muscle.

[Effect of glutamate on membrane potential and volume of the skeletal muscle fibers in rats following NO-synthase inhibition in vivo]. / Vliianie glutamata na membrannyi potentsial i ob''em skeletnykh myshechnykh volokon krysy posle blokady NO-sintazy in vivo.

Cross-sectional area (CSA) of muscle fibers incubated in culture medium 199 for 3 hours dramatically increases, whereas resting membrane potential (RMP) decreases compared to "freshly-isolated" muscles. Both glutamate and sodium nitroprusside prevent these changes. MK-801, a specific inhibitor of NMDA-receptors, eliminates protective effects of glutamate on both CSA and RMP. NO-synthase inhibition in vivo promotes an increase of initial CSA and decrease of mean RMP. Under these conditions, effects of glutamate and sodium nitroprusside on CSA and RMP of denervated muscles are less obvious. It has been concluded that synaptic glutamate is able to participate in regulation of RMP and cell volume in muscle fibers through the activation of postsynaptic NMDA-receptors and muscle NO-synthase.

[Effect of glutamate on spontaneous secretion of acetylcholine in the nerve-muscle synapse in rats]. / Vliianie glutamata na protsessy spontannoi sekretsii atsetilkholina v nervno-myshechnom sinapse krysy.

In rats, glutamate was shown to exert no effect on the mean frequency, character of interstimuli distribution, amplitude and temporal parameters of the miniature EPPs. Glutamate suppressed nonquantal release. The glutamate effect depended on its concentration and was abolished by blockade of NMDA receptors, NO-synthase inhibitoin, and NO molecules binding by haemoglobin in extracellular medium. Glutamate seems to modulate the nonquantal acetylcholine secretion by initiation of the NO synthesis in muscle fibres via activation of the NMDA receptors.

[Synthesis and release of N-acetylaspartyl glutamate (NAAG) in medial giant axons in crayfish]. / Sintez i osvobozhdenie N-acetylaspartylglutamate (NAAG) v sredinnykh gigantskikh aksonakh raka.

Studies of crayfish Medial Giant nerve Fiber suggested that glutamate (GLU) released from the axon during action potential generation initiates metabolic and electrical responses of periaxonal glia. This investigation sought to elucidate the mechanism of GLU appearance extracellularly following axon stimulation. Axoplasm and periaxonal glial sheath from nerve fibers incubated with radiolabelled L-GLU contained radiolabeled GLU, glutamine (GLN), GABA, aspartate (ASP), and NAAG. Total radiolabel release was not altered by electrical stimulation of nerve cord loaded with [14C]-GLU by bath application or loaded with [14C]-GLU, [3H]-D-ASP, or [3H]-NAAG by axonal injection. However, radioactivity distribution among GLU and its metabolic products in the superfusate was changed, with NAAG accounting for the largest fraction. In axons incubated with radiolabeled GLU, the stimulated increase in radioactive NAAG in the superfusate coincided with the virtual clearance of radioactive NAAG from the axon. The increase in [3H]-GLU in the superfusion solution that was seen upon stimulation of nerve bathloaded with [3H]-NAAG was reduced when beta-NAAG, a competitive NAALADase inhibitor, was present. Together, these results suggest that some GLU is metabolized to NAAG in the giant axon and its periaxonal glia and that, upon stimulation, NAAG is released and converted to GLU by NAALADase. A quisqualate-, beta-NAAG-sensitive NAALADase activity was detected in nerve cord homogenates. Stimulation or NAAG administration in the presence of NAALADase inhibitor caused a transient hyperpolarization of the periaxonal glia comparable to that produced by L-GLU. The results implicate N-acetylaspartylglutamate (NAAG) and GLU as potential mediators. of the axon-glia interactions.

[Modulation of the intensity of the non-quantal transmitter release by nitric oxide (NO) at the neuromuscular junction]. / Moduliatsiia intensivnosti nekvantovoi sekretsii mediatora v nervno-myshechnom soedinenii krysy oksidom azota (NO).

In the rat diaphragm muscle, nitric oxide (NO)--sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP), as well as substrate for the NO synthesis L-arginine, decrease the level of hyperpolarization of the muscle fibre membrane after acetylcholine receptor blockade by the d-TC and irreversible acetylcholinesterase inhibition by armin (H-effect). Contrary to that, disruption of the NO synthesis in the muscle fibres by the NO-synthase inhibitor NG-nitrol-L-arginine methyl ester (L-NAME) results in enhancement of the H-effect both in vitro and in vivo. Inactivated SNP and inactive forms of arginine and NAME did not affect the H-effect magnitude. Haemoglobin, effectively binding the NO molecules, abolishes the suppressing effects of the SNP, SNAP and L-arginine upon the H-effect. The findings suggest that the NO could be acting as a modulator of nonquantal transmitter release at the mammalian neuromuscular junction.

[The physiological role of nitric oxide]. / Fiziologicheskaia rol' oksida azota.

The review is devoted to exposition of a physiological role of a nitric oxide (NO), free radical gas, in various physiological functions. The number of those NO involvements is extremely high: bacteriocidal, cytotoxic and antitumor leukocyte effects, a relaxation of smooth-muscle cells of both vessels and gastrointestinal tract, the name just a few. The scheme of NO formation in various biological systems and its targets were shown and neuromodulator functions of NO in a brain were analyzed by the review presented. The findings of own researches on a role of NO in function of neuro-muscular synapse were included by the authors.

Carnosine and other imidazole-containing compounds enhance the postdenervation depolarization of the rat diaphragm fibres.

In the presence of carnosine, anserine, histidine, imidazole and 7-nitro indazole, the early postdenervation depolarization of muscle of about 8 mV was significantly increased by 2.15-4.8 mV. The presence of the imidazole ring in the molecule is apparently necessary for this effect. These compounds also eliminated an NO-mediated protective effect of L-glutamate and carbachol on the depolarization of membrane potential. The presence of imidazole, 7-nitro indazole, carnosine and anserine did not significantly change the effect of an external NO donor, sodium nitroprusside. The structural and functional similarity between imidazole derivatives and the known NO synthase inhibitor, 7-nitro indazole suggests that imidazole, carnosine and anserine might act by inhibiting NO production which is stimulated by glutamate and carbachol.

[The sodium-potassium-chloride cotransport of the cell membrane]. / Natrii-kalii-khlornyi kotransport kletochnoi membrany.

Discovery and active exploration of the furosemid-sensitive derived-active co-transport of sodium-potassium-chlorine ions took place in the end of 1970-es-1980-es. This transportation mechanism was discovered in various types of cells, both of plant and of animal origin. This review describes properties of the transportation process, which was most comprehensive explored in experiments with erythrocytes, epithelium cells and muscles. The review covers the following properties: anion and cation selectivity of the chlorine transportation, its sensitivity to the specific blocking agents (furocemid, bumetanid, etc.), stoichiometry of the transportation process, etc. For energy source, the chlorine transportation is based on transmembrane electrochemical gradient for sodium ions. The article provides the most recent results of investigation of the chemical nature of the molecule of the chlorine membrane transport. Based on various studies, the molecule of this protein weighs from 120 to 200 kD, includes about 1200 amino acid residua, and forms long cytoplasmatic NH2 and COOH-termini. The gene encoding the amino acid sequence has been cloned. The article discusses the issues of regulation of the chlorine transportation. Humoral control of intensity of the chlorine transportation has been mostly studied in experiments with plain muscles, the issues related to nervous regulation--with only skeleton muscle fibers. The article provides specific data on the mechanisms of the above types of the physiological regulation of active chlorine transportation. In general, the humoral factors, which increase the intracellular concentration of cAMF stimulate chlorine transportation. On the contrary, the hormones, which increase concentration of cGMF in cytoplasm reduce its activity in plain muscles. The discussion of the mechanisms of the nervous controls of the chlorine transportation in the skeleton muscles includes the original results of the author. These results indicate that the suppressive influence of the motor innervation on intensity of the chlorine transportation involves the non-quantum acetilcholine and glutamate secreted from the motor nerves. These agents produce Ca(2+)-dependent molecules of nitrogen oxide in sarcoplasm, which act in the retrograde mode on the nervous terminal and activate there the synthesis of cGMF. Disruption of this bilateral transsynaptic signalization resulting from cutting a nerve of blocking of its axoflow creates more active chlorine transportation and subsequent de-innervation changes in properties of the muscle fibers. The functions of chlorine transportation, which are best studies as of today and therefore, discussed in more detail in the review, include participation of this process in the regulatory rehabilitation of the volume of various cells in non-isotonic medium, and the role of chlorine transportation in development of a negative charge at the interior side of membrane of the skeleton muscle fibers. The former function essentially means that dehydration of a cell in the hypertonic medium increases activity of the sodium, potassium and chlorine co-transport directed to the cell, resulting in increase of the amount of the osmosis-active cytoplasm material, and inflow of water, which fully restores the cell volume in these conditions. Starting from the pioneer studies by Hodgkin and Horowicz [correction of Hojkin and Gorovits], the role of chlorine ions in forming a charge on the membrane of excited cells has been generally interpreted as exclusively passive. I.e., distribution of these ions over both sides of membrane was assumed as equilibrium with the existing values of the membrane potential in the non-excited state. The review provides data obtained in the recent decade, which have proved that the non-excited membrane potential in muscle fibers is co-created by the diffusional potassium and chlorine potential. (ABSTRACT TRUNCATED)

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. It follows that the effect of glutamate on early post-denervation 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 x 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.

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.

[L-glutamate--a candidate for the role of membrane-potential nerve control factor in mammalian muscle fibers]. / L-glutamat--pretendent na rol' faktora nervnogo kontrolia membrannogo potentsiala v myshechnykh voloknakh mlekopitaiushchikh.

L-glutamate released from the motor nerve terminal seems to be involved in the maintenance of resting potential (RP) in skeletal muscles via the N-methyl-D-aspartate (NMDA)-activated influx of Ca2+ to the cytoplasm with subsequent activation of NO-synthase and production of the NO which could act as a messenger providing the control of the membrane ion-transporting proteins.

[Neurotrophic control of the ionic regulation mechanisms for intracellular water content in muscle fibers of mammals]. / Neirotroficheskii kontrol' ionnykh mekhanizmov reguliatsii vnutrikletochnogo soderzhaniia vody v myshechnykh voloknakh mlekopitaiushchikh.

The volume change of the muscle fibres in the hypertonic medium begins with cell shrinkage. Later the cell volume increases up to the normal level because of the furosemide-sensitive CL(-)-influx activation. The property of the Cl(-)-influx to be activated in the hypertonic medium is abolished after denervation. That causes a loss of the ability of muscle fibres to restore their cell volume in the hypertonic medium.

[Effects of hyperosmolarity and furosemide on resting membrane potentials and skeletal muscle fiber volume in rats]. / Vliianie giperosmoliarnosti i furosemida na membrannyi potentsial pokoia i ob"em skeletnykh myshechnykh volokon krysy.

The changes of the muscle fibres volume and resting membrane potential (RMP) were studied following treatment with hypertonic medium and furosemide. The volume changes in hypertonic medium began with cell shrinkage and later have been followed by the volume increase up to normal level during 30-40 minutes. At the same time the medium hypertonicity caused muscle fibres depolarisation. The hypertonic-induced decrease of the RMP was delayed in the furosemide-treated muscle. Besides, furosemide abolished the muscle fibres volume restorative properties in hypertonic medium. It is suggested that the membrane depolarisation and cell volume restoration in hypertonic medium are the resultant effects of intracellular chloride ions level elevation which, in turn, have been evoked by activation of furosemide-sensitive Cl(-)-influx system.