Effect of I<inf>Ca,L</inf> blockade on adrenergic stimulation in developing heart

© 2016 Springer Science+Business Media New York.The effect of verapamil-induced blockade of L-type calcium ionic currents (ICa,L) on the action of non-selective adrenergic cardiac stimulation by norepinephrine was examined during different periods of early postnatal ontogeny. In 1-week-old rats, intravenous norepinephrine induced a short-term tachycardia both with and without preliminary injected verapamil. In 3-week-old rats, norepinephrine alone produced no chronotropic effect; in contrast, it induced a biphasic tachycardia in verapamil-treated rats. In 6- and 20-month-old rats, norepinephrine induced a short-term tachycardia, which could be prevented by verapamil. The age-related peculiarities of chronotropic action of non-selective adrenergic stimulation are indicative of the role of L-type calcium ionic channels in the development of sympathetic control over the heart

Effects of a hydrogen sulfide donor on spontaneous contractile activity of rat stomach and jejunum

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. © 2014 Springer Science+Business Media

Peculiarities of synaptic vesicle recycling in frog and mouse motor nerve terminals

Using electrophysiology and fluorescence microscopy with dye FM 1-43, a comparative study of peculiarities of neurotransmitter secretion, synaptic vesicle exo-endocytosis and recycling has been carried out in nerve terminals (NT) of the skin-sternal muscle of the frog Rana ridibunda and of the white mouse diaphragm muscle during a long-term high-frequency stimulation (20 imp/s). The obtained data have allowed identifying three synaptic vesicle pools and two recycling ways in the motor NT. In the frog NT, the long-term high-frequency stimulation induced consecutive expenditure of the pool ready to release, the mobilizational, and reserve vesicle pools. The exocytosis rate exceeded markedly the endocytosis rate; the slow synaptic vesicle recycling with replenishment of the reserve pool was predominant. In the mouse NT, only the vesicles of the ready to release and the mobilizational pools, which are replenished predominantly by fast recycling, were exocytosed. The exo- and endocytosis occurred practically in parallel, while vesicles of the reserve pool did not participate in the neurotransmitter secretion. It is suggested that evolution of the motor NT from the poikilothermal to homoiothermal animals went by the way of a decrease of the vesicle pool size, the more economic expenditure and the more effective reuse of synaptic vesicles owing to the high rates of endocytosis and recycling. These peculiarities can provide in NT of homoiothermal animals a long maintenance of neurotransmitter secretion at the steady and sufficiently high level to preserve reliability of synaptic transmission in the process of the high-frequency activity. © 2008 Pleiades Publishing, Ltd

Peculiar effects of muscarinic M1, M2, and M3 receptor blockers on cardiac chronotropic function in neonatal rats.

The effects of muscarinic M(1), M(2), and M(3) cholinergic receptor blockade on the regulation of chronotropic function of the heart were studied in vivo in 7-day-old rat pups. Intravenous injection of M(2) receptor blocker gallamine produced no changes in cardiac chronotropy. In contrast, M(1) receptor blocker pirenzepine and M(3) receptor blocker 4DAMP provoked bradycardia. These data attest to the involvement of M(1) and especially M(3) cholinergic receptors in the regulation of cardiac chronotropy in rat pups, which confirms the view on pronounced species-specific and age-related peculiarities in the heart control mechanisms

Peculiar effects of muscarinic M1, M2, and M 3 receptor blockers on cardiac chronotropic function in neonatal rats

Department of Anatomy, Physiology, and Human Health Protection, Kazan (Volga Region) Federal University, Russia The effects of muscarinic M 1, M2, and M3 cholinergic receptor blockade on the regulation of chronotropic function of the heart were studied in vivo in 7-day-old rat pups. Intravenous injection of M2 receptor blocker gallamine produced no changes in cardiac chronotropy. In contrast, M1 receptor blocker pirenzepine and M3 receptor blocker 4DAMP provoked bradycardia. These data attest to the involvement of M1 and especially M3 cholinergic receptors in the regulation of cardiac chronotropy in rat pups, which confirms the view on pronounced species-specific and age-related peculiarities in the heart control mechanisms. © 2012 Springer Science+Business Media New York

Cellular and receptor mechanisms of impairment of myocardium and aorta contractility at Alzheimer's disease model

Introduction: Recent studies certify the existence of link between Alzheimer's disease and cardiovascular pathology, however the mechanisms of this phenomenon is unclear. Here we studied the influence of Alzheimer's β-amyloid peptide (βAP) on the contractility of rat myocardium and aorta. Material and methods: Contractility of myocardium ventricle strips and transverse fragments of abdominal aorta was measured at Power Lab setup using conventional myographic technique. Contractile responses of aorta strips were evoked by application of receptor agonists, contractile responses of myocardium - by electrical stimulation. Contractile responses of aorta strips after application of carbachol (10-6-10-4 M), histamine (10 -6-10-4 M), norepinephrine (10-5-10 -3 M) and ATP (10-6-10-4 M) were measured. Results and discussion: We found the impairment of carbachol- and histamine-induced contractility of aorta, appearing as perverse contractile reactions (relaxation instead of contraction) under the action of βAP (10-6 M). Next, we found βAP-induced impairments of ventricle myocardium contractility, appearing as decrease of relaxation phase duration and increase of relaxation speed (positive lusitropic effect). Also, own positive lusitropic effect of norepinephrine was absent in presence of βAP (10 -6M). Thus, βAP(25-35) significantly impairs the contractility of rat myocardium and aorta, as well as processes of its regulation. Obtained data significantly broad our understanding of mechanisms of Alzheimer's disease pathogenesis and pathophysiology of cardiovascular system

Ketamine-Midazolam Anesthesia Induces Total Inhibition of Cortical Activity in the Brain of Newborn Rats

© 2016, Springer Science+Business Media New York.The effects of general anesthetics ketamine and midazolam, the drugs that cause neuroapoptosis at the early stages of CNS development, on electrical activity of the somatosensory cortex in newborn rats were studied using extracellular recording of local field potentials and action potentials of cortical neurons. Combined administration of ketamine (40 mg/kg) and midazolam (9 mg/kg) induced surgical coma and almost completely suppressed early oscillatory patterns and neuronal firing. These effects persisted over 3 h after injection of the anesthetics. We concluded that general anesthesia induced by combined administration of ketamine and midazolam profoundly suppressed cortical activity in newborn rats, which can trigger neuroapoptosis in the developing brain

Intravenous Transplantation of Human Umbilical Cord Blood Mononuclear Cells Overexpressing Nerve Growth Factor Improves Spatial Memory in APP/PS1 Transgenic Mice with a Model of Alzheimer’s Disease

© 2017, Springer Science+Business Media, LLC, part of Springer Nature. Alzheimer’s disease is a progressive incurable neurodegenerative disease manifested by dementia and other cognitive disorders. Gene-cell therapy is one of the most promising trends in the development of treatment for Alzheimer’s disease. The study was aimed to evaluate the therapeutic potential of intravenous transplantation of human umbilical cord blood mononuclear cells (UCBMCs) transduced with adenoviral vectors overexpressing nerve growth factor (NGF) for the treatment of Alzheimer’s disease in an APP/PS1 transgenic mice model. The transplantation of NGF-expressing UCBMCs was found to improve spatial memory and decrease anxiety in APP/PS1 mice. Grafted cells and their expression of NGF were detected in the cortex and hippocampus of transgenic mice in the period up to 90 days after transplantation. Thus, gene-cell therapy based on the use of NGF-overexpressing UCBMCs is a promising approach for the development of Alzheimer’s disease treatments

Modulation of neurotransmitter release by carbon monoxide at the frog neuro-muscular junction

Carbon monoxide (CO) is an endogenous gaseous messenger, which regulates numerous physiological functions in a wide variety of tissues. Using extracellular microelectrode recording from frog neuro-muscular preparation the mechanisms of exogenous and endogenous CO action on evoked quantal acetyl-choline (Ach) release were studied. It was shown that CO application increases Ach-release in dose-dependent manner without changes in pre-synaptic Na+ and K+ currents. The effect of exogenous CO on Ach-release was decreased by prior application of guanylate cyclase inhibitor ODQ and prevented by application of a cyclic guanylate monophospate (cGMP) analog 8Br-cGMP. Pre-treatment of the preparation with adenylate cyclase inhibitor MDL-12330A has completely abolished the effect of CO, whereas elevation of intracellular level of cyclic adenosine monophospate (cAMP) mimicked and eliminated CO action. Application of cGMP-activated phosphodiestherase-2 inhibitor EHNA did not prevent CO action, whereas inhibition of cGMP-inhibited phosphodiestherase-3 by quazinone has partially blocked the effect of CO. Utilizing immuno-histochemical methods CO-producing enzyme heme-oxygenase-2 (HO-2) was shown to be expressed in skeletal muscle fibers, mostly in subsarcolemmal region, karyolemma and sarcoplasmic reticulum. Zn-protoporphirin-IX, the selective HO-2 blocker, has depressed Ach-release, suggesting the tonic activating effect of endogenous CO on pre-synaptic function. These results suggest that facilitatory effect of CO on Ach-release is mediated by elevation of intracellular cAMP level due to activation of adenylate cyclase and decrease of cAMP breakdown. As such, endogenous skeletal muscle-derived CO mediates tonic retrograde up-regulation of neuro-transmitter release at the frog neuro-muscular junction. © 2007 Bentham Science Publishers Ltd

Mechanisms of hydrogen sulfide (H<inf>2</inf>S) action on synaptic transmission at the mouse neuromuscular junction

© 2015 IBRO. Hydrogen sulfide (H2S) is a widespread gasotransmitter also known as a powerful neuroprotective agent in the central nervous system. However, the action of H2S in peripheral synapses is much less studied. In the current project we studied the modulatory effects of the H2S donor sodium hydrosulfide (NaHS) on synaptic transmission in the mouse neuromuscular junction using microelectrode technique. Using focal recordings of presynaptic response and evoked transmitter release we have shown that NaHS (300μM) increased evoked end-plate currents (EPCs) without changes of presynaptic waveforms which indicated the absence of NaHS effects on sodium and potassium currents of motor nerve endings. Using intracellular recordings it was shown that NaHS increased the frequency of miniature end-plate potentials (MEPPs) without changing their amplitudes indicating a pure presynaptic effect. Furthermore, NaHS increased the amplitude of end-plate potentials (EPPs) without influencing the resting membrane potential of muscle fibers. l-cysteine, a substrate of H2S synthesis induced, similar to NaHS, an increase of EPC amplitudes whereas inhibitors of H2S synthesis (β-cyano-l-alanine and aminooxyacetic acid) had the opposite effect. Inhibition of adenylate cyclase using MDL 12,330A hydrochloride (MDL 12,330A) or elevation of cAMP level with 8-(4-chlorophenylthio)-adenosine 3′,5′-cyclic monophosphate (pCPT-cAMP) completely prevented the facilitatory action of NaHS indicating involvement of the cAMP signaling cascade. The facilitatory effect of NaHS was significantly diminished when intracellular calcium (Ca2+) was buffered by 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis acetoxymethyl ester (BAPTA-AM) and ethylene glycol-bis(2-aminoethylether)-N,N,N′,N′-tetraacetic acid acetoxymethyl ester (EGTA-AM). Activation of ryanodine receptors by caffeine or ryanodine increased acetylcholine release and prevented further action of NaHS on transmitter release, likely due to an occlusion effect. Inhibition of ryanodine receptors by ryanodine or dantrolene also reduced the action of NaHS on EPC amplitudes. Our results indicate that in mammalian neuromuscular synapses endogenously produced H2S increases spontaneously and evoked quantal transmitter release from motor nerve endings without changing the response of nerve endings. The presynaptic effect of H2S appears mediated by intracellular Ca2+ and cAMP signaling and involves presynaptic ryanodine receptors