Primary gamma-rays with E gamma or = to 10(15) eV: Evidence for ultrahigh energy particle acceleration in galactic sources

The recently observed primary ultra high energy gamma-rays (UHEGR) testify to the cosmic ray (CR) acceleration in the Galaxy. The available data may be interpreted as gamma-ray production due to photomeson production in CR sources

Modern Concepts of Cholinergic Neurotransmission at the Motor Synapse

© 2018, Pleiades Publishing, Ltd. Cholinergic synaptic contact between motor neuron and skeletal muscle fiber is perhaps one of the core objects for investigations of molecular mechanisms underlying the communication between neurons and innervated cells. In the studies conducted on this object in the past few decades, a large amount of experimental data was obtained that substantially complemented a traditional view on synaptic transmission. In particular, it was established that (i) acetylcholine is released from the nerve ending in both quantal and nonquantal ways; (ii) molecular mechanisms of the processes of the quantal acetylcholine release—spontaneous and evoked by electrical stimuli—have unique features and can be regulated independently; (iii) acetylcholine release from the nerve ending is accompanied by a release of a number of synaptically active molecules modulating the processes of secretion or reception of the main mediator; (iv) signal molecules affecting the process of cholinergic neurotransmission can be released not only from the nerve ending but also from glial cells and muscle fiber; (v) molecular mechanisms of the regulation of synaptic transmission are highly diverse and go beyond the alteration of the number of the released acetylcholine quanta. Thus, the neuromuscular junction shall be deemed currently as complicated and adaptive synapse characterized by a wide range of multiloop intercellular signaling pathways between presynaptic motor neuron ending, muscle fiber, and glial cells ensuring a high safety factor of synaptic transmission and the possibility of its fine tuning

Excitatory effects of GABA during ontogeny

Gamma-aminobutyric acid (GABA) is the main inhibitory transmitter in the central nervous system. However, at the early stages of development, GABA has excitatory influences on immature neurons. This review presents contemporary views on the mechanisms of GABAergic excitation and the physiological role of excitatory GABA in generating patterns of network activity in the developing brain. © 2013 Springer Science+Business Media New York

Autoregulation of acetylcholine release and micro-pharmacodynamic mechanisms at neuromuscular junction: Selective acetylcholinesterase inhibitors for therapy of myasthenic syndromes

© 2018 Petrov, Nikolsky and Masson. Neuromuscular junctions (NMJs) are directly involved into such indispensable to life processes as respiration and locomotion. However, motor nerve forms only one synaptic contact at each muscle fiber. This unique configuration requires specific properties and constrains to be effective. The very high density of acetylcholine receptors (AChRs) of muscle type in synaptic cleft and an excess of acetylcholine (ACh) released under physiological conditions make this synapse extremely reliable. Nevertheless, under pathological conditions such as myasthenia gravis and congenital myasthenic syndromes, the safety factor can be markedly reduced. Drugs used for short-term symptomatic therapy of these pathological states, cause partial inhibition of cholinesterases (ChEs). These enzymes catalyze the hydrolysis of ACh, thus terminate its action on AChRs. Extension of the lifetime of ACh molecules compensates muscular AChRs abnormalities and, consequently, rescues muscle contractions. In this mini review, we will first outline the functional organization of the NMJ, and then, consider the concept of the safety factor and how it may be changed. This will be followed by a look at autoregulation of ACh release that influences the safety factor of NMJs. Finally, we will consider the morphological features of NMJs as a putative reserve to increase effectiveness of pathological muscle weakness therapy by ChEs inhibitors due to opportunity to use micro-pharmacodynamic mechanisms

Contribution of Ryanodine Receptors in Forming Presynaptic Ca²⁺ Level and Cholinergic Modulation in Response to Single Potential in Frog Neuromuscular Junction

© 2016, Springer Science+Business Media New York.Ca2+ entering through voltage-gated Ca2+ channels plays a key role in the initiation of neurotransmitter secretion. However, intracellular Ca2+ storages such as endoplasmic reticulum (ER) can also contribute in the presynaptic Ca2+ level forming. Also ryanodine-dependent Ca2+-induced Ca2+ channels of endoplasmic reticulum may contribute in secretion inhibiting action of cholinomimetics. In this work, we use a photometric method for estimating the relative change in the level of presynaptic Ca2+ ions (Ca2+ transient). We have shown that during low-frequency stimulation Ca2+ release from the ER is involved in forming of presynaptic Ca2+ level. And more likely those effects of the cholinomimetics on Ca2+ transient are not related to Ca2+ release from the endoplasmic reticulum

Presynaptic nicotinic cholinoreceptors modulate velocity of the action potential propagation along the motor nerve endings at a high-frequency synaptic activity

© 2016, Pleiades Publishing, Ltd.Experiments on frog neuromuscular junctions have demonstrated that asynchrony of the acetylcholine quantal release forming the multi-quantal evoked response at high-frequency synaptic activity is caused, in particular, by a decrease in velocity of the action potential propagation along the non-myelinated nerve endings, which is mediated by activation of the α7 and α4β4 nicotinic cholinoreceptors

Solvothermal Synthesis of Sm3+-doped Fe3O4 nanoparticles

Magnetic iron oxide nanoparticles doped with samarium were prepared by solvothermal polyol method. An introduction of 2,2'-bipyridine during the synthesis reduces the particle diameter to about 9 nm in average. The difference in physical and magnetic properties of the samples prepared with and without capping agent was outlined on the basis of complex characterization by a number of experimental techniques. The characteristics of resulted product make it suitable for biomedical applications, for instance, as a contrast agent for MR

Immunohistochemical evidence of the presence of metabotropic receptors for γ-aminobutyric acid at the rat neuromuscular junctions

© 2015, Pleiades Publishing, Ltd. in the synapses of the “fast” (m. EDL) and “slow” (m. soleus) skeletal muscles of the rat GABABR1 and GABABR2 subunits of metabotropic receptors for γ-aminobutyric acid (GABA), located primarily on the motor nerve ending membrane were detected by immunohistochemistry and fluorescence microscopy methods

Effect of Noradrenaline on the Kinetics of Evoked Acetylcholine Secretion in Mouse Neuromuscular Junction

© 2018, Pleiades Publishing, Ltd. Abstract: In contrast to frog neuromuscular synapses, where noradrenaline (norepinephrine) and its analogues caused synchronization of the acetylcholine release process, in mouse diaphragm endplates noradrenaline increased the degree of asynchrony of neurosecretion. The effect of noradrenaline on release timing persisted at different levels of external calcium ions (0.25–2.0 mM) and was abolished in presence of both α- and β‑adrenoblockers phentolamine and propranolol. The computer reconstruction of multiquantal endplate currents accounting for experimentally observed modification of release kinetics under noradrenaline showed that the rise time of postsynaptic response changes to a greater extent than the amplitude and falling phase of the multiquantal responses. We conclude that there exists a principal difference in the action of noradrenaline in the cholinergic neuromuscular synapses of warm-blooded and cold-blooded animals that can be accounted for by the differences in the type of adrenoreceptors involved in the modulation of synaptic transmission and/or in the involvement of distinct intracellular pathways triggered by receptor activation