Impairment of Skeletal Muscle Contraction by Inhibitors of GABA Transporters.

γ-Aminobutyric acid (GABA) has a significant impact on the functioning of not only the central but also the peripheral part of the nervous system. Recently, various elements of the GABAergic signaling system have been discovered in the area of the neuromuscular junction of mammals. At the same time, the functional activity of membrane-bound GABA transporters (GATs) and their role in neuromuscular transmission have not been identified.

Protective properties of melanin from lichen Lobaria pulmonaria (L.) HOFFM. In models of oxidative stress in skeletal muscle.

Melanin is a dark pigment from the group of phenolic or indole polymers with inherent biocompatibility and antioxidant capacity. In extremophilic lichen Lobaria pulmonaria, melanin is responsible for protective properties against hostile environments. Herein, the ability of melanin extracted from L.

β2-Adrenergic Regulation of the Neuromuscular Transmission and Its Lipid-Dependent Switch.

β2-Adrenoceptors (β2-ARs) are the most abundant subtype of adrenergic receptors in skeletal muscles. Their activation via a stabilization of postsynaptic architecture has beneficial effects in certain models of neuromuscular disorders. However, the ability of β2-ARs to regulate neuromuscular transmission at the presynaptic level is poorly understood.

Effects of cholesterol oxidase on neurotransmission and acetylcholine levels at the mice neuromuscular junctions.

Membrane cholesterol oxidation is a hallmark of redox and metabolic imbalance, and it may accompany neurodegenerative disorders. Using microelectrode recordings of postsynaptic responses as well as fluorescent dyes for monitoring synaptic vesicle cycling and membrane properties, the action of enzymatic cholesterol oxidation on neuromuscular transmission was studied in the mice diaphragms. Cholesterol oxidase (ChO) at low concentration disturbed lipid-ordering specifically in the synaptic membranes, but it did not change markedly spontaneous exocytosis and evoked release in response to single stimuli.

Activation of TRPV1 Channels Inhibits the Release of Acetylcholine and Improves Muscle Contractility in Mice.

TRPV1 represents a non-selective transient receptor potential cation channel found not only in sensory neurons, but also in motor nerve endings and in skeletal muscle fibers. However, the role of TRPV1 in the functioning of the neuromuscular junction has not yet been fully established. In this study, the Levator Auris Longus muscle preparations were used to assess the effect of pharmacological activation of TRPV1 channels on neuromuscular transmission.

Differentiation of Myoblasts in Culture: Focus on Serum and Gamma-Aminobutyric Acid.

There are many facts about the possible role of gamma-aminobutyric acid (GABA) in the development and differentiation of cells not only in nervous but also in muscle tissue. In the present study, a primary culture of rat skeletal muscle myocytes was used to evaluate the correlation between the content of GABA in the cytoplasm and the processes of myocyte division and their fusion into myotubes. The effect of exogenous GABA on the processes of culture development was also estimated.

Sphingomyelinase modulates synaptic vesicle mobilization at the mice neuromuscular junctions.

Aims: Sphingomyelin is an abundant component of the presynaptic membrane and an organizer of lipid rafts. In several pathological conditions, sphingomyelin is hydrolyzed due to an upregulation and release of secretory sphingomyelinases (SMases). Herein, the effects of SMase on exocytotic neurotransmitter release were studied in the diaphragm neuromuscular junctions of mice.

Activation of Neuronal Nicotinic Receptors Inhibits Acetylcholine Release in the Neuromuscular Junction by Increasing Ca Flux through Ca1 Channels.

Cholinergic neurotransmission is a key signal pathway in the peripheral nervous system and in several branches of the central nervous system. Despite the fact that it has been studied extensively for a long period of time, some aspects of its regulation still have not yet been established. One is the relationship between the nicotine-induced autoregulation of acetylcholine (ACh) release with changes in the concentration of presynaptic calcium levels.

GABA in developing rat skeletal muscle and motor neurons.

In recent years, considerable evidence is accumulated pointing to participation of gamma-aminobutyric acid (GABA) in intercellular signaling in the peripheral nervous system, including, in particular, neuromuscular transmission. However, where in the neuromuscular synapse GABA is synthesized remains not quite clear. We used histochemical methods to detect GABA and L-glutamate decarboxylase (GAD) in developing skeletal muscle fibers and in cultured motor neurons.

Components of the GABAergic signaling in the peripheral cholinergic synapses of vertebrates: a review.

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian central nervous system. Since the 1970s, many studies have focused on the role of GABA in the mammalian peripheral nervous system, and particularly in the cholinergic synapses. In this review, we present current findings for the cholinergic neurons of vegetative ganglia as well as for the neurons innervating smooth and striated muscles.

Enhancement of mouse diaphragm contractility in the presence of antagonists of GABA and GABA receptors.

New Findings: What is the central question of this study? Do GABA receptors play any role at the neuromuscular junction? What is the main finding and its importance? In the presence of either ionotropic or metabotropic GABA receptor antagonists, diaphragm muscle force production elicited by stimulating the motor nerve at ≥50 Hz was increased. Our data indicate the presence of GABAergic signalling at the neuromuscular junction.

Abstract: Despite the signalling role of GABA in the brain and spinal cord, the role of this molecule in the peripheral nervous system and, in particular, at the neuromuscular junction remains practically unexplored.

Elements of molecular machinery of GABAergic signaling in the vertebrate cholinergic neuromuscular junction.

It is generally accepted that gamma-aminobutyric acid (GABA) is a signaling molecule abundant in central synapses. In a number of studies though, it has been shown that GABA signaling functions in the peripheral nervous system as well, in particular, in the synapses of sympathetic ganglia. However, there exists no firm evidence on the presence of GABAergic signaling cascade in the intercellular junctions of the somatic nerve system.

Metabotropic and ionotropic glutamate receptors mediate the modulation of acetylcholine release at the frog neuromuscular junction.

There is some evidence that glutamate (Glu) acts as a signaling molecule at vertebrate neuromuscular junctions where acetylcholine (ACh) serves as a neurotransmitter. In this study, performed on the cutaneous pectoris muscle of the frog Rana ridibunda, Glu receptor mechanisms that modulate ACh release processes were analyzed. Electrophysiological experiments showed that Glu reduces both spontaneous and evoked quantal secretion of ACh and synchronizes its release in response to electrical stimulation.

Metabotropic GABAB receptors mediate GABA inhibition of acetylcholine release in the rat neuromuscular junction.

Gamma-aminobutyric acid (GABA) is an amino acid which acts as a neurotransmitter in the central nervous system. Here, we studied the effects of GABA on non-quantal, spontaneous, and evoked quantal acetylcholine (ACh) release from motor nerve endings. We found that while the application of 10 μM of GABA had no effect on spontaneous quantal ACh release, as detected by the frequency of miniature endplate potentials, GABA reduced the non-quantal ACh release by 57%, as determined by the H-effect value.

Regulation of acetylcholinesterase activity by nitric oxide in rat neuromuscular junction via N-methyl-D-aspartate receptor activation.

Acetylcholinesterase (AChE) is an enzyme that hydrolyses the neurotransmitter acetylcholine, thereby limiting spillover and duration of action. This study demonstrates the existence of an endogenous mechanism for the regulation of synaptic AChE activity. At the rat extensor digitorum longus neuromuscular junction, activation of N-methyl-d-aspartate (NMDA) receptors by combined application of glutamate and glycine led to enhancement of nitric oxide (NO) production, resulting in partial AChE inhibition.

NMDA receptors at the endplate of rat skeletal muscles: precise postsynaptic localization.

In this study we demonstrate expression of the N-methyl-D-aspartate receptor NR1 subunit in the rat neuromuscular junction of skeletal muscles of different functional types (extensor digitorum longus, soleus, and diaphragm muscles) using fluorescence immunocytochemistry. Electron microscopic immunocytochemistry has shown that the NR1 subunit is localized solely on the sarcolemma in the depths of the postsynaptic folds. These findings suggest participation of the glutamatergic signaling system in functioning of the adult mammalian neuromuscular junction.

Purine P2Y receptors in ATP-mediated regulation of non-quantal acetylcholine release from motor nerve endings of rat diaphragm.

We established the effect of ATP, which is released together with acetylcholine (ACh), on the non-quantal ACh release (NQR) in rat diaphragm endplates and checked what kind of purine receptors are involved. NQR was estimated by the amplitude of endplate hyperpolarization (the H-effect) following the blockade of postsynaptic nicotinic receptors and cholinesterase. 100 μM ATP reduced the H-effect to 66% of the control.

Muscarinic M1 acetylcholine receptors regulate the non-quantal release of acetylcholine in the rat neuromuscular junction via NO-dependent mechanism.

Nitric oxide (NO), previously demonstrated to participate in the regulation of the resting membrane potential in skeletal muscles via muscarinic receptors, also regulates non-quantal acetylcholine (ACh) secretion from rat motor nerve endings. Non-quantal ACh release was estimated by the amplitude of endplate hyperpolarization (H-effect) following a blockade of skeletal muscle post-synaptic nicotinic receptors by (+)-tubocurarine. The muscarinic agonists oxotremorine and muscarine lowered the H-effect and the M1 antagonist pirenzepine prevented this effect occurring at all.

Effect of N-acetylaspartylglutamate (NAAG) on non-quantal and spontaneous quantal release of acetylcholine at the neuromuscular synapse of rat.

N-Acetylaspartylglutamate (NAAG), known to be present in rat motor neurons, may participate in neuronal modulation of non-quantal secretion of acetylcholine (ACh) from motor nerve terminals. Non-quantal release of ACh was estimated by the amplitude of the endplate membrane hyperpolarization (H-effect) caused by inhibition of nicotinic receptors by (+)-tubocurarine and acetylcholinesterase by armin (diethoxy-p-nitrophenyl phosphate). Application of exogenous NAAG decreased the H-effect in a dose-dependent manner.

Glutamate regulation of non-quantal release of acetylcholine in the rat neuromuscular junction.

Glutamate, previously demonstrated to participate in regulation of the resting membrane potential in skeletal muscles, also regulates non-quantal acetylcholine (ACh) secretion from rat motor nerve endings. Non-quantal ACh secretion was estimated by the amplitude of endplate hyperpolarization (H-effect) following blockade of skeletal muscle post-synaptic nicotinic receptors by (+)-tubocurarine and cholinesterase by armin (diethoxy-p-nitrophenyl phosphate). Glutamate was shown to inhibit non-quantal release but not spontaneous and evoked quantal secretion of ACh.