Comparative Analysis of Cardiac Effects of α<inf>1A</inf>-Adrenoreceptor Stimulation In Vivo and Ex Vivo in Newborn Rats

© 2020, Springer Science+Business Media, LLC, part of Springer Nature. The study examined the effects of α1A-adrenoceptor stimulation on chronotropic function of Langendorff-perfused isolated heart ex vivo and on cardiac chronotropy in vivo in 7-day-old rats. α1A-Adrenergic receptor agonist A-61603 reduced heart chronotropy only in the whole organism. No chronotropic effects of selective stimulation of α1A-adrenergic receptors on isolated hearts were observed in ex vivo experiments. These findings suggest that α1A-adrenergic receptors are not implicated in HR regulation in newborn rats. Bradycardia induced by activation of these receptors in vivo is most likely associated with reflex influences on the heart and changes in the vascular tone in the whole organism

Effect of Clonidine Hydrochloride on Isolated Newborn Rat Heart

The concentration dependenies of the chronotropic response and changes in blood supply to the isolated heart of 7-day-old newborn rats induced by application of α2-adrenergic receptor agonist clonidine hydrochloride in concentrations of 10-9-10-6 M were revealed. The minimum concentration of α2-adrenergic receptor agonist caused tachycardia, while higher concentrations led to bradycardia. The maximum effect manifesting in a decrease in coronary flow was recorded at the minimum concentration of the agonist, while the highest concentration had no effect on the coronary flow. When comparing these results with those obtained in control adult rats, we found that the most pronounced differences in the chronotropic effects were observed after addition of the minimum concentration of the α2-adrenergic receptor agonist: bradycardia in adult rats and tachycardia in newborns. The maximum differences in coronary flow parameters were observed after addition of α2-adrenergic receptor agonist in the maximum concentration that induced a two-phase response in adult rats and had no effect on the blood supply in newborns

Correction to: Peculiar Aspects in Influence of α<inf>1</inf>-Adrenoceptor Stimulation on Isolated Rat Heart (Bulletin of Experimental Biology and Medicine, (2016), 162, 1, (4-6), 10.1007/s10517-016-3530-z)

Correction to the article “Peculiar Aspects in Influence of α1-Adrenoceptor Stimulation on Isolated Rat Heart,” by T. L. Zefirov, I. I. Khabibrakhmanov, N. I. Ziyatdinova, and A. L. Zefirov, Vol. 162, No. 1, pp. 4-6, November 2016

Effects of Homocysteine and its Derivatives on Spontaneous Network Activity in the Hippocampus of Neonatal Rat Pups

© 2020, Springer Science+Business Media, LLC, part of Springer Nature. Homocysteine is a sulfur-containing amino acid, which at high concentrations has neurotoxic effects and induces impairments to the development of the nervous system. Homocysteine is rapidly oxidized in the plasma, forming disulfide bonds with proteins and other low molecular weight thiols; it also undergoes transformation into the into homocysteine thiolactone. On chronic exposure, the neurotoxicity of homocysteine is therefore mediated mainly by its derivatives. The aim of the present work was to investigate the effects of homocysteine and its derivatives – homocystine and homocysteine thiolactone – on spontaneous network activity in the hippocampus of rats in the first week after birth. Giant depolarizing potentials (GDP) and multiple action potentials (MAP) were recorded using an extracellular electrode in hippocampal field CA3. All three study compounds were found to induce increases in the frequency of GDP and MAP at concentrations of 100 and 500 μM, homocystine producing the most significant increase in neuron network activity. The effects of homocysteine, homocystine, and homocysteine thiolactone on the spontaneous network activity of neurons were completely eliminated on blockade of NMDA and AMPA receptors. Thus, homocysteine and its derivatives lead to increased spontaneous network activity of hippocampal neurons in neonatal rats, which can induce impairments to the formation of the neural networks of the hippocampus in conditions of chronic hyperhomocysteinemia, and could also induce hyperexcitability and the risk of developing epilepsy in the postnatal period

Intracellular Acidification Suppresses Synaptic Vesicle Mobilization in the Motor Nerve Terminals

Copyright © 2020 National Research University Higher School of Economics. Intracellular protons play a special role in the regulation of presynaptic processes, since the functioning of synaptic vesicles and endosomes depends on their acidification by the H+-pump. Furthermore, transient acidification of the intraterminal space occurs during synaptic activity. Using microelectrode recording of postsynaptic responses (an indicator of neurotransmitter release) and exo-endocytic marker FM1-43, we studied the effects of intracellular acidification with propionate on the presynaptic events underlying neurotransmitter release. Cytoplasmic acidification led to a marked decrease in neurotransmitter release during the first minute of a 20-Hz stimulation in the neuromuscular junctions of mouse diaphragm and frog cutaneous pectoris muscle. This was accompanied by a reduction in the FM1-43 loss during synaptic vesicle exocytosis in response to the stimulation. Estimation of the endocytic uptake of FM1-43 showed no disruption in synaptic vesicle endocytosis. Acidification completely prevented the action of the cell-membrane permeable compound 24-hydroxycholesterol, which can enhance synaptic vesicle mobilization. Thus, the obtained results suggest that an increase in [H+]in negatively regulates neurotransmission due to the suppression of synaptic vesicle delivery to the sites of exocytosis at high activity. This mechanism can be a part of the negative feedback loop in regulating neurotransmitter release