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Your search keyword '"Alexander V. Maltsev"' showing total 2 results
Start Over Author "Alexander V. Maltsev" Publisher mdpi ag
2 results on '"Alexander V. Maltsev"'

1. Structure-Function Relationship of the Ryanodine Receptor Cluster Network in Sinoatrial Node Cells

Author

Alexander V. Maltsev, Valeria Ventura Subirachs, Oliver Monfredi, Magdalena Juhaszova, Pooja Ajay Warrier, Shardul Rakshit, Syevda Tagirova, Anna V. Maltsev, Michael D. Stern, Edward G. Lakatta, and Victor A. Maltsev

Subjects
β adrenergic stimulation, numerical model, pacemaker function, ryanodine receptor, sinoatrial node, Cytology, QH573-671
Abstract

The rate of spontaneous action potentials (APs) generated by sinoatrial node cells (SANC) is regulated by local Ca2+ release (LCR) from the sarcoplasmic reticulum via Ca2+ release channels (ryanodine receptors, RyRs). LCR events propagate and self-organize within the network of RyR clusters (Ca release units, CRUs) via Ca-induced-Ca-release (CICR) that depends on CRU sizes and locations: While larger CRUs generate stronger release signals, the network’s topology governs signal diffusion and propagation. This study used super-resolution structured illumination microscopy to image the 3D network of CRUs in rabbit SANC. The peripheral CRUs formed a spatial mesh, reflecting the cell surface geometry. Two distinct subpopulations of CRUs were identified within each cell, with size distributions conforming to a two-component Gamma mixture model. Furthermore, neighboring CRUs exhibited repulsive behavior. Functional properties of the CRU network were further examined in a novel numerical SANC model developed using our experimental data. Model simulations revealed that heterogeneities in both CRU sizes and locations facilitate CICR and increase the AP firing rate in a cooperative manner. However, these heterogeneities reduce the effect of β-adrenergic stimulation in terms of its relative change in AP firing rate. The presence of heterogeneities in both sizes and locations allows SANC to reach higher absolute AP firing rates during β-adrenergic stimulation. Thus, the CICR facilitation by heterogeneities in CRU sizes and locations regulates and optimizes cardiac pacemaker cell operation under various physiological conditions. Dysfunction of this optimization could be a key factor in heart rate reserve decline in aging and disease.

Published
2024
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2. Amyloid Aβ25-35 Aggregates Say ‘NO’ to Long-Term Potentiation in the Hippocampus through Activation of Stress-Induced Phosphatase 1 and Mitochondrial Na+/Ca2+ Exchanger

Author

Alexander V. Maltsev, Anna B. Nikiforova, Natalia V. Bal, and Pavel M. Balaban

Subjects
Inorganic Chemistry, Organic Chemistry, General Medicine, Physical and Theoretical Chemistry, amyloid peptides, Alzheimer’s disease, field excitatory postsynaptic potentials, nitric oxide, serine/threonine phosphatases, mitochondrial Na+/Ca2+ exchanger, Molecular Biology, Spectroscopy, Catalysis, Computer Science Applications
Abstract

The search for strategies for strengthening the synaptic efficiency in Aβ25-35-treated slices is a challenge for the compensation of amyloidosis-related pathologies. Here, we used the recording of field excitatory postsynaptic potentials (fEPSPs), nitric oxide (NO) imaging, measurements of serine/threonine protein phosphatase (STPP) activity, and the detection of the functional mitochondrial parameters in suspension of brain mitochondria to study the Aβ25-35-associated signaling in the hippocampus. Aβ25-35 aggregates shifted the kinase–phosphatase balance during the long-term potentiation (LTP) induction in the enhancement of STPP activity. The PP1/PP2A inhibitor, okadaic acid, but not the PP2B blocker, cyclosporin A, prevented Aβ25-35-dependent LTP suppression for both simultaneous and delayed enzyme blockade protocols. STPP activity in the Aβ25-35-treated slices was upregulated, which is reverted relative to the control values in the presence of PP1/PP2A but not in the presence of the PP2B blocker. A selective inhibitor of stress-induced PP1α, sephin1, but not of the PP2A blocker, cantharidin, is crucial for Aβ25-35-mediated LTP suppression prevention. A mitochondrial Na+/Ca2+ exchanger (mNCX) blocker, CGP37157, also attenuated the Aβ25-35-induced LTP decline. Aβ25-35 aggregates did not change the mitochondrial transmembrane potential or reactive oxygen species (ROS) production but affected the ion transport and Ca2+-dependent swelling of organelles. The staining of hippocampal slices with NO-sensitive fluorescence dye, DAF-FM, showed stimulation of the NO production in the Aβ25-35-pretreated slices at the dendrite-containing regions of CA1 and CA3, in the dentate gyrus (DG), and in the CA1/DG somata. NO scavenger, PTIO, or nNOS blockade by selective inhibitor 3Br-7NI partly restored the Aβ25-35-induced LTP decline. Thus, hippocampal NO production could be another marker for the impairment of synaptic plasticity in amyloidosis-related states, and kinase–phosphatase balance management could be a promising strategy for the compensation of Aβ25-35-driven deteriorations.

Published
2022
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