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Fedorenko Y.A.,Bogomolets Institute of Physiology of the NAS of Ukraine | Fedorenko Y.A.,State Key Laboratory of Molecular and Cellular Biology
Neurophysiology | Year: 2016

Inositol 1,4,5-trisphosphate receptors (IP3Rs) play a key role in intracellular calcium signaling. Up to the present time, the question on the existence of only one level of the unitary conductance of such receptors or a few levels of such conductance remained open. In experiments on the isolated nuclei of Purkinje cerebellar neurons of rats, we examined changes in the conductance of channels of these receptors localized on the internal membrane of the nuclear envelope, which were related to voltage variations. In all cases, these channels demonstrated only one level of the unitary conductance; no sublevels were found within a –100 mV to 100 mV range. Suppression of activity of IP3Rs at negative potentials is determined by a decrease in the probability of the open state of the channel. Thus, a hypothesis on the existence of a few levels of the IP3R channel conductance in the examined object has not been confirmed; the release of Ca2+ through channels of these receptors demonstrates a quantum nature. © 2016 Springer Science+Business Media New York


Kulyk V.B.,Bogomolets Institute of Physiology of the NAS of Ukraine | Volkova T.N.,Bogomolets Institute of Physiology of the NAS of Ukraine | Kryshtal' O.A.,Bogomolets Institute of Physiology of the NAS of Ukraine
Neurophysiology | Year: 2016

The topic of this review is the current understanding of the mechanisms of neuro-immune interactions responsible for suppression of pain by endogenous opioids. Special attention is paid to the events occurring in peripheral tissues after injury, excitation of high-threshold afferent inputs, and generation of nociceptive impulsation. The release of opioid peptides from immune cells migrating to the focus of inflammation and “inhabiting” the latter provides (at least partially) significant reduction of the excitability of nociceptive sensory neurons. Exogenous opioid ligands that do not cross the bloodbrain barrier also selectively modulate the excitability of primary afferents. Thus, sensory neurons in the peripheral tissues are an essential target for the action of endogenous opioids. There are reasons to believe that the clinical use of peripherally acting opioids can help one to substantially avoid the negative side effects caused by the action of conventional analgesics (opioids and anticonvulsants). Modern concepts on the mechanisms of secretion and release of peripherally acting opioids and their effects on inflammation and pain, the role of the immune response in antinociception, and prospects for the use of the above opioids in the treatment of pain-related phenomena are discussed. © 2016 Springer Science+Business Media New York


Maznychenko A.V.,Bogomolets Institute of Physiology of the NAS of Ukraine
Neurophysiology | Year: 2014

We detected changes in the gene c-fos expression induced by activation of muscle afferents in the rat spinal cord after systemic introduction of reserpine (irreversible suppressor of vesicular transporter of monoamines, 1.5 mg/kg, intraperitoneally) and with no action of this agent. Numbers of Fosimmunoreactive (Fos-ir) neurons were calculated in the gray matter of the lumbar spinal segments after unilateral vibrational stimulation (VS) of the Achilles tendon of the mm. gastrocnemius–soleus. In the spinal cord of rats preliminarily injected with reserpine, greater numbers of Fos-ir neurons were observed; these units were localized mostly in layers 4–7 and in the nucl. intermediolateralis (35.4 ± 1.6 and 16.7 ± 0.9 positive neurons per 40 μm-thick slice) of segments L1–L2, and also in layers 4–7 and layer 9 (Fos-ir motoneurons) of segments L4–L5 (51.7 ± 3.4 and 11.4 ± 1.5 labeled units, respectively). The numbers of activated cells in the above structures of the spinal cord after VS but without preliminary injections of reserpine were, on average, 25.6 ± 1.4 and 3.5 ± 0.5, 27.8 ± ± 0.9 and 6.9 ± 0.3 units, respectively. Most ipsilateral Fos-ir motoneurons (86%) were localized in the lateral pool of layer 9, and only 14% of labeled motoneurons were localized in its medial regions. The results obtained show that weakening of monoaminergic influences resulting from administration of reserpine is accompanied by increase in the activity of intraspinal neuronal networks activated by proprioceptive afferent volleys, and the effects of the above inputs on spinal motoneurons and sympathetic preganglionic neurons are intensified. Weakening of inhibitory control, realized by inhibitory interneurons in the pathways of transmission of excitatory influences from muscle afferents to motoneurons, which was observed in our experiments after suppression of monoaminergic modulatory systems, can be considered a significant factor responsible for the development of rigidity/spasticity of the limb muscles manifested in neurodegenerative diseases and after traumas of the spinal cord. © 2015, Springer Science+Business Media New York.


Rybachuk O.A.,Bogomolets Institute of Physiology of the NAS of Ukraine | Pivneva T.A.,Bogomolets Institute of Physiology of the NAS of Ukraine
Neurophysiology | Year: 2013

Mesenchymal stem cells, MSCs, were identified in the 1960s. Recently, these cells have attracted great attention from researchers because their clinical applications look rather promising. At present, MSCs are most frequently interpreted as multipotent cells characterized by fibroblast-like morphology and capable of proliferating. These are non-differentiated cells possessing a great potential for differentiation and formation of tissues of different types, including the bone, cartilage, and muscle tissues, and also of the bone marrow stroma. In accessible publications, there is information that extremely wide plasticity is typical of MSCs obtained from the bone marrow; these cells can serve as originating units for the nerve tissue, hepatocytes, cardiomyocytes, and epithelial cells of the lungs. In this review, we describe results of recent studies in the field of fundamental biology of MSCs separated from different sources, their identification, potential for differentiation, and possibilities for therapeutic use. © 2013 Springer Science+Business Media New York.


Magura I.S.,Bogomolets Institute of Physiology of the NAS of Ukraine | Bogdanova N.A.,Bogomolets Institute of Physiology of the NAS of Ukraine | Dolgaya E.V.,Bogomolets Institute of Physiology of the NAS of Ukraine
Neurophysiology | Year: 2013

Dendrites provide the analysis and transmission of numerous and variable synaptic signals to the soma and axon hillock of nerve cells. According to generally accepted concepts, generation of action potentials (APs) is initiated precisely in the latter cell compartment. The problem of the dynamics of functioning of voltage-operated ion channels, whose properties are extremely variable, is closely related to the integrative functions of the dendrites. These channels are involved in information transmission and its translation to other domains of the neuron. The biophysical properties of dendrite ion channels and the density of their distribution in many cases differ significantly from the analogous indices in other compartments of the neuron. Moreover, the expression of ion channels and their properties in different branches of the dendrite tree of one and the same neuron can be considerably dissimilar. Such phenomena as back-propagation of APs via the dendrites and the possible initiation of local APs in some branches of the dendrite tree are significantly involved in the induction of synaptic plasticity; these processes may result in either augmentation of synaptic potentials or their suppression. Local synthesis of definite proteins is also realized in the dendrites; this process is controlled by synaptic inputs and postsynaptic activity. The possibility of performance of a few integrative functions by separate dendrites of a single neuron is at present intensely discussed; earlier, such functions were postulated to be a prerogative of complex neuronal networks. © 2013 Springer Science+Business Media New York.


Fisyunov A.I.,Bogomolets Institute of Physiology of the NAS of Ukraine
Neurophysiology | Year: 2012

Receptors of the 7-TMR group (G protein-coupled receptors, GPCRs) are uniquely important from the fundamental physiological aspect because they mediate the effects of a majority of the known neuromediators and hormones. According to a widely accepted paradigm, activation of heterotrimetric G proteins is the initial step in the process of transduction of signals from these receptors to effectors. In recent times, increasing proof of the existence of G protein-independent mechanisms providing initiation of biochemical signals by these receptors and modulation of the excitability of the neurons has been accumulated. According to these data, 7-TMRs are able to interact with a few cytoplasmic scaffold proteins and take part in various protein-to-protein interactions. Despite the fact that functional importance of many such interactions remains unknown at present, the respective results indicate that the above processes are capable not only of providing G protein-independent transmission of signals from the 7-TMRs, but also of influencing pharmacological characteristics, cellular localization, and compartmentalization of the mentioned receptors. © 2012 Springer Science+Business Media, Inc.


Gura Y.V.,Bogomolets Institute of Physiology of the NAS of Ukraine | Bagatskaya Y.V.,Bogomolets Institute of Physiology of the NAS of Ukraine
Neurophysiology | Year: 2015

In experiments on male albino mice, we examined the role of the serotonergic cerebral system in analgesia induced by microwave irradiation of the acupuncture point (AP) E-36. Two modes of irradiation were used: broadband (30–300 GHz) radiation with low-frequency (0.1–100 Hz) amplitude modulation and fixed-frequency (61 ± 4 GHz) radiation. Irradiation of the AP preceded induction of visceral pain by i.p. injections of acetic acid. A blocker of serotonin (ST) synthesis, DL para-chlorophenylalanine (PCPA, 300 mg/kg), introduced 72 h before injection of acetic acid, provided significant prolongation of manifestations of the pain behavioral reaction (PBR) by 41.6 and 66.7%, respectively, as compared with the duration of this reaction in mice subjected to irradiation of the AP in the above modes but with no PCPA injection (P < 0.05 in both cases). Intensification of the PBR against the background of blockade of ST synthesis shows that the respective cerebral system is significantly involved in analgesia induced by preliminary (preceding the induction of the pain syndrome) microwave irradiation of the AP E-36. © 2015, Springer Science+Business Media New York.


Kulyk V.B.,Bogomolets Institute of Physiology of the NAS of Ukraine | Chizhmakov I.V.,Bogomolets Institute of Physiology of the NAS of Ukraine | Volkova T.M.,Bogomolets Institute of Physiology of the NAS of Ukraine | Kryshtal' O.A.,Bogomolets Institute of Physiology of the NAS of Ukraine
Neurophysiology | Year: 2015

As is traditionally believed, the analgesic effects of opioids are due to their action on the CNS mechanisms. At present, however, proofs are been accumulated that activation of opioid receptors at the periphery can also result in a strong analgesic effect (especially in the case of inflammatory processes). In neurons of the dorsal root ganglia (DRG) of rats, we examined the effects of activation of opioid receptors on purinergic (P2X3) receptor-mediated ion currents and tried to identify possible intracellular signal pathways between the respective receptors. P2X3-mediated ion currents in DRG neurons were evoked by applications of αβ-Me-ATP. These currents were strongly (on average, by 74%) and reversibly inhibited after application of an endogenous opioid peptide, leu-enkephalin (L-Enk, 100 nM). A selective competitive antagonist of μ opioid receptors, CTOP, completely abolished the effect of L-Enk. We believe that a pathway mediated by phospholipase C (PLC) is involved in intracellular signaling between opioid and P2X3 receptors, and our experiments confirmed this hypothesis. A synthetic activator of PLC suppressed P2X3-mediated currents; an inhibitor of synthesis of phosphatidylinositol 4,5-bisphosphate (PIP2), wortmannin, accelerated and augmented the inhibitory effect of L-Enk on P2X3-mediated currents. Therefore, the inhibitory effect of L-Enk on the latter receptors is based on activation on PLC and hydrolysis of PIP2. © 2015, Springer Science+Business Media New York.


Bagatskaya Ye.V.,Bogomolets Institute of Physiology of the NAS of Ukraine | Gura Ye.V.,Bogomolets Institute of Physiology of the NAS of Ukraine
Neurophysiology | Year: 2013

We studied the effects of preliminary irradiation of the acupuncture point (AP) E36 by low-intensity microwaves on experimentally evoked somatic pain in mice. Irradiation preceded induction of somatic pain in the formalin test, FT (subcutaneous injection of 25 μl 5% formalin solution into the dorsal surface of the foot).The FT was carried out in different groups of animals immediately, 10 min, and 20 min after termination of a period of microwave irradiation of the AP. Analgesic effects were observed in all examined animal groups within both acute and tonic pain phases. Normalized decreases in the duration of behavioral manifestations of the acute pain phase were equal to 57.7, 50.4, and 28.8% in the cases where the FT was realized immediately, 10 min, and 20 min after irradiation of the AP. For the tonic phase of the pain reaction, the respective figures were 49.6, 60.5, and 56.2%, respectively. Thus, irradiation of the AP E36 by low-intensity microwaves performed before the development of somatic pain exerts noticeably stronger hypoalgesic effects with respect to tonic somatic pain. © 2013 Springer Science+Business Media New York.


Maistrenko A.M.,Bogomolets Institute of Physiology of the NAS of Ukraine | Kopach O.V.,Bogomolets Institute of Physiology of the NAS of Ukraine | Skibo G.G.,Bogomolets Institute of Physiology of the NAS of Ukraine
Neurophysiology | Year: 2015

This review describes the peculiarities of the molecular structure of hypoxia-inducible factor (HIF) and the mechanisms of activation of a complex including HIF, a key factor of adaptation of the cell to ischemic and hypoxic injuries. The tissue specificity of expression of different subtypes of the α HIF subunit and most typical target genes activated by this complex are described. In addition, the specificities of HIF-mediated cell responses related to ischemic damage (the latter, at present, forms one of the main medical/clinical problems) are analyzed; the expedience and prospects of further studies of the signal pathways involving the mentioned transcription factor are emphasized. © 2015, Springer Science+Business Media New York.

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