Сведения о наиболее значимых научных результатах НИР и публикации (монографии, статьи и тезисы)
О НАУЧНО-ИССЛЕДОВАТЕЛЬСКОЙ РАБОТЕ за 2014 год [pdf файл]
О НАУЧНО-ИССЛЕДОВАТЕЛЬСКОЙ РАБОТЕ за 2013 год [pdf файл]
О НАУЧНО-ИССЛЕДОВАТЕЛЬСКОЙ РАБОТЕ за 2012 год [pdf файл]
Главные публикации за 2014
Sitdikova GF, Fuchs R, Kainz V, Weiger TM and Hermann A Phosphorylation of BK channels modulates the sensitivity to hydrogen sulfide (H2S). Front. Physiol 2014. 5:431. [Link]
Gases, such as nitric oxide (NO), carbon monoxide (CO), or hydrogen sulfide (H2S), termed gasotransmitters, play an increasingly important role in understanding of how electrical signaling of cells is modulated. H2S is well-known to act on various ion channels and receptors. In a previous study we reported that H2S increased calcium-activated potassium (BK) channel activity. AIMS: The goal of the present study is to investigate the modulatory effect of BK channel phosphorylation on the action of H2S on the channel as well as to recalculate and determine the H2S concentrations in aqueous sodium hydrogen sulfide (NaHS) solutions. METHODS:Single channel recordings of GH3, GH4, and GH4 STREX cells were used to analyze channel open probability, amplitude, and open dwell times. H2S was measured with an anion selective electrode. RESULTS:The concentration of H2S produced from NaHS was recalculated taking pH, temperature salinity of the perfusate, and evaporation of H2S into account. The results indicate that from a concentration of 300 μM NaHS, only 11-13%, i.e., 34-41 μM is effective as H2S in solution. GH3, GH4, and GH4 STREX cells respond differently to phosphorylation. BK channel open probability (Po) of all cells lines used was increased by H2S in ATP-containing solutions. PKA prevented the action of H2S on channel Po in GH4 and GH4 STREX, but not in GH3 cells. H2S, high significantly increased Po of all PKG pretreated cells. In the presence of PKC, which lowers channel activity, H2S increased channel Po of GH4 and GH4 STREX, but not those of GH3 cells. H2S increased open dwell times of GH3 cells in the absence of ATP significantly. A significant increase of dwell times with H2S was also observed in the presence of okadaic acid. CONCLUSIONS: Our results suggest that phosphorylation by PKG primes the channels for H2S activation and indicate that channel phosphorylation plays an important role in the response to H2S.
E. Dyukova, G. Sitdikova, R. Schreckenberg, Y. Abdallah, K.D. Schlüter Mechanisms by which calcium receptor stimulation modifies electromechanical coupling in isolated ventricular cardiomyocytes Pflügers Archiv - European Journal of Physiology February 2015, Volume 467, Issue 2, pp 379-388
The calcium-sensing receptor (CaR) is widely expressed throughout the entire cardiovascular system and is capable of activating signaling pathways in different cells. Alongside calcium, the CaR also responds to physiological polycations such as putrescine underlining a participation in physiological and pathophysiological processes. Here, we aimed to determine mechanisms as to how CaR activation affects the contractile responsiveness of ventricular cardiomyocytes under basal and stimulated conditions. For that purpose, cardiac myocytes from 3-month-old male Wistar rats were isolated, and the acute effects of an antagonist (NPS2390), agonists (putrescine and gadolinium), or of downregulation of the CaR by siRNA on cell shortening were recorded in a cell-edge-detection system. In addition, experiments were performed on muscle stripes and Langendorff preparations. Mechanistic insights were taken from calcium transients of beating fura-2 AM-loaded cardiomyocytes and western blots. Isolated ventricular cardiomyocytes constitutively express CaR. The expression in the atria is less pronounced. Acute inhibition of CaR reduced basal cell shortening of ventricular myocytes at nearly physiological levels of extracellular calcium. Inhibition of CaR strongly reduced contractility of ventricular muscle stripes but not of atria. Activation of CaR by putrescine and gadolinium influences the contractile responsiveness of isolated cardiomyocytes. Increased calcium mobilization from the sarcoplasmic reticulum via an IP3-dependent mechanism was responsible for amplified systolic calcium transients and a subsequent improvement in cell shortening. Alongside with these effects, activation of CaR increased relaxation velocity of the cells. In conclusion, ventricular CaR expression affects contractile parameters of ventricular heart muscle cells and modifies electromechanical coupling of cardiomyocytes.
M. Y. Shafigullin, R. A. Zefirov*, G. I. Sabirullina, A. L. Zefirov, and G. F. Sitdikova Effects of a Hydrogen Sulfi de Donor on Spontaneous Contractile Activity of Rat Stomach and Jejunum. Bulletin of Experimental Biology and Medicine, Vol. 157, No. 3, July, 2014 PHYSIOLOGY P302-306
We studied the effect of sodium hydrosulfite (NaHS), a donor of hydrogen sulfide (H2S), on spontaneous contractive activity of isolated preparations of rat stomach and jejunum under isometric conditions. NaHS in concentrations of 10-200 μM reduced the amplitude, tonic tension, and frequency of contractions of the preparations. Blockade of K+ channels with a non-specific antagonist tetraethylammonium (10 mM) increased contraction amplitude in the stomach strip and jejunum segment. The effects of NaHS on all parameters of contractile activity of the stomach and jejunum were fully preserved against the background of tetraethylammonium application. These data suggest that H2S in physiologically relevant concentrations inhibited spontaneous contractile activity of smooth muscle cells in rat stomach and jejunum by reducing the amplitude and frequency of contractions and decreased tonic tension without affecting the function of voltage- and calcium-dependent K+ channels.
T. V. Baltina, M. V. Kuznetsov, A. A. Yeremeev, and M. E. Baltin. Effect of Vibratory Stimulation of Foot Support Areas in Rats on the Functional State of Leg Muscles and the Content of N2A Titin Isoforms in Gravity Relief // Biophysics.- 2014.- V. 59, No2. - P. 316–320. ISSN 00063509
In this work, we studied the effect of vibratory stimulation of the foot support zones on the functional state of the leg muscles and the content of N2A titin isoforms in rats under simulated microgravity (suspension model). The results of this study showed that vibratory stimulation of the support zones of the rat foot in a gravity discharge may reduce the drop in the amplitude of leg muscle motor response and undesirable reduction of the titin content.
Guzel Sitdikova, Andrei Zakharov, Sona Janackova, Elena Gerasimova, Julia Lebedeva, Ana R. Inacio, Dilyara Zaynutdinova, Marat Minlebaev, Gregory L. Holmes, Roustem Khazipov; Isoflurane suppresses early cortical activity Annals of Clinical and Translational Neurology 2014; 1(1): 15–26 PDF
Objective Isoflurane and other volatile anesthetics are widely used in children to induce deep and reversible coma, but they may also exert neurotoxic actions. The effects of volatile anesthetics on the immature brain activity remain elusive, however.Methods The effects of isoflurane on spontaneous and sensory-evoked activity were explored using intracortical extracellular field potential and multiple unit recordings in the rat barrel cortex from birth to adulthood.Results During the first postnatal week, isoflurane suppressed cortical activity in a concentration-dependent manner. At surgical anesthesia levels (1.5–2%), isoflurane completely suppressed the electroencephalogram and silenced cortical neurons. Although sensory potentials evoked by the principal whisker deflection persisted, sensory-evoked early gamma and spindle-burst oscillations were completely suppressed by isoflurane. Isoflurane-induced burst-suppression pattern emerged during the second postnatal week and matured through the first postnatal month. Bursts in adolescent and adult rats were characterized by activation of entire cortical columns with a leading firing of infragranular neurons, and were triggered by principal and adjacent whiskers stimulation, and by auditory and visual stimuli, indicating an involvement of horizontal connections in their generation and horizontal spread.Interpretation The effects of isoflurane on cortical activity shift from total suppression of activity to burst-suppression pattern at the end of the first postnatal week. Developmental emergence of bursts likely involves a development of the intracortical short- and long-range connections. We hypothesize that complete suppression of cortical activity under isoflurane anesthesia during the first postnatal week may explain neuronal apoptosis stimulated by volatile anesthetics in the neonatal rats.
Cuellara, C.A. Spinal neurons bursting in phase with fictive scratching are not related to spontaneous cord dorsum potentials/ C.A. Cuellara, A. Trejo, P. Linares, R. Delgado-Lezama, I. Jiménez-Estrada, L.M. Abyazova, T.V. Baltina, E.Manjarrez. //Neuroscience.-V.266,No4 – 2014.- P.66–79
Spontaneous cord dorsum potentials (spontaneous CDPs) are produced by the activation of dorsal horn neurons distributed along the L4 to S1 spinal cord segments, in Rexed's laminae III-VI, in the same region in which there are interneurons rhythmically bursting during fictive scratching in cats. An interesting observation is that spontaneous CDPs are not rhythmically superimposed on the sinusoidal CDPs generated during fictive scratching episodes, thus suggesting that the interneurons producing both types of CDPs belong to different spinal circuits. In order to provide experimental data to support this hypothesis, we recorded unitary activity of neurons in the L6 spinal cord segment. We found that the neurons firing rhythmically during the sinusoidal CDPs associated with the extensor, flexor or intermediate phases of scratching were not synchronized with the spontaneous CDPs. Moreover, we found that the neurons firing during the spontaneous CDPs were not synchronized with the sinusoidal CDPs. These results suggest that the neurons involved in the occurrence of spontaneous CDPs are not part of the spinal cord central pattern generators (CPGs). This study will be relevant for understanding the relationships between the spinal cord neuronal populations firing spontaneously and the CPGs, in the intact and injured spinal cord.