Biology subjects

Bychkov, R.

Publications and source records attributed to Bychkov, R..

3 recordsLinked to original sources

bioRxiv2024

Unique spatiotemporal synchronization solutions of heterogeneous local Ca2+ dynamics underlie the formation of each impulse that emerges from the cardiac sinoatrial node

We used both linear and nonlinear analyses to determine how information processing within and among incessant heterogeneous local Ca2+ oscillation (LCO) results in formation of rhythmic impulses in mouse SAN ex vivo. Phase analysis delineated a network of functional pacemaker cell clusters, distinguished by their LCO amplitudes, kinetics, and phases. Cross-talk of LCO dynamics within the network culminated in rhythmic SAN global Ca2+ transients (CaTs), having a mean rate and rhythm identical to that recorded by the reference sharp electrode in the right atria, indicating that CaTs are induced by global SAN electrical impulses. Initial conditions of each impulse and subsequent LCO ensemble evolution during an impulse differed from each other, associated with an apparent stochastic process (carrying a degree of uncertainty) within network. A small pacemaker cluster located near the crista terminalis (CT) exhibited the highest degrees of intrinsic power, earliest rotor-like energy transfer, most frequent point-to-point instability, earliest acrophase, greatest impulse-to-impulse variability within the SAN functional cluster network. Unique, variable small-world network Ca2+ information sharing within and among all clusters during initial and terminal impulse phases, created a unique solution for each impulse, while preserving the identity of each cluster (a highly efficient form of information processing at low wiring and energy costs). Cross-recurrence analysis verified that LCO dynamics within the small cluster near CT were more stochastic and less deterministic than those of the other clusters, indicating that this small cluster took the lead in the initiation of the SAN impulse and that the others followed.

cell biology↗

bioRxiv2022

The Heart's Pacemaker Mimics Brain Cytoarchitecture and Function: Autonomic innervation, a peripheral glial cell web, and a novel S100B expressing interstitial cell type impart structural and functional complexity to the sinoatrial node

ObjectivesThis study sought to describe the 3D cytoarchitecture of sinoatrial node tissue, including autonomic innervation, peripheral glial cells, and pacemaker cells. BackgroundThe sinoatrial node of the heart produces rhythmic action potentials (AP), generated via calcium signaling within and among pacemaker cells. Our previous work has described the SAN as composed of an HCN4-expressing pacemaker cell meshwork, which merges with a network of CX43+/F-actin+ cells. It is also known that sympathetic and parasympathetic innervation from epicardial ganglia create an autonomic plexus in the sinoatrial node, which modulates heart rate and rhythm. However, the anatomical details of the interaction of this plexus with the pacemaker cell meshwork have yet to be described. Methods3D confocal laser-scanning microscopy of triple immunolabeled SAN whole mount preparations with combinations of antibodies for HCN4, S100B, GFAP, ChAT or VAChT, and TH, and transmission electron microscopy (TEM). ResultsThe SAN exhibited heterogeneous autonomic innervation, which was accompanied by a web of peripheral glial cells (PGCs). Further, we identified a novel S100B+/GFAP- interstitial cell population, with unique morphology and distinct distribution pattern, creating complex interactions with other cell types in the node. TEM images showed a similar population of cells, here identified as telocytes, which appeared to secrete vesicles towards pacemaker cells. Application of S100B protein to SAN preparations induced distinct changes in rhythmogenic calcium signaling. ConclusionsThe autonomic plexus and its associated peripheral glial cell web, a novel network of S100B expressing interstitial cells resembling telocytes, and a meshwork of HCN4+ cells interact to impart structural complexity to the sinoatrial node. Summary Table [Table 1][Table 1]

physiology↗

bioRxiv2020

Synchronized cardiac impulses emerge from multi-scale, heterogeneous local calcium signals within and among cells of heart pacemaker tissue

ABSTRACTBackground The current paradigm of Sinoatrial Node (SAN) impulse generation: (i) is that full-scale action potentials (APs) of a common frequency are initiated at one site and are conducted within the SAN along smooth isochrones; and (ii) does not feature fine details of Ca2+ signalling present in isolated SAN cells, in which small subcellular, subthreshold local Ca2+ releases (LCRs) self-organize to generate cell-wide APs.Objectives To study subcellular Ca2+ signals within and among cells comprising the SAN tissue.Methods We combined immunolabeling with a novel technique to detect the occurrence of LCRs and AP-induced Ca2+ transients (APCTs) in individual pixels (chonopix) across the entire mouse SAN images.Results At high magnification, Ca2+ signals appeared markedly heterogeneous in space, amplitude, frequency, and phase among cells comprising an HCN4+/CX43- cell meshwork. The signalling exhibited several distinguishable patterns of LCR/APCT interactions within and among cells. Apparently conducting rhythmic APCTs of the meshwork were transferred to a truly conducting HCN4-/CX43+ network of straited cells via narrow functional interfaces where different cell types intertwine, i.e. the SAN anatomical/functional unit. At low magnification, the earliest APCT of each cycle occurred within a small area of the HCN4 meshwork and subsequent APCT appearance throughout SAN pixels was discontinuous.Conclusions We have discovered a novel, microscopic Ca2+ signalling paradigm of SAN operation that has escaped detection using low-resolution, macroscopic tissue isochrones employed in prior studies: APs emerge from heterogeneous subcellular subthreshold Ca2+ signals, resembling multiscale complex processes of impulse generation within clusters of neurons in neuronal networks.Condensed abstract By combining immunolabeling with a novel optical technique we detected markedly heterogenous Ca2+signals within and among cell clusters of an HCN4+/CX43- meshwork in mouse sinoatrial node. These Ca2+ signals self-organized and transferred, throughout the node, to projections from an HCN4-/CX43+ network connected to a highly organized, rapidly conducting part of the CX43+ network. Thus, APs emerge from heterogeneous, subthreshold Ca2+ signaling not detected in low-resolution macroscopic isochrones. Our discovery requires a fundamental paradigm shift from concentric impulse propagation initiated within a leading site, to a multiscale/complex process, resembling the emergence of organized signals from heterogeneous local signals within neuronal networks.Competing Interest StatementThe authors have declared no competing interest.Abbreviations listAPaction potentialAPCTAP-induced Ca2+ transientChronopixchrono-pixelCX43Connexin 43 (Gap junction alpha-1 protein)FFTFast Fourier TransformHCN4Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 4ICaLL-type Ca2+ currentICaTT-type Ca2+ currentIVCInferior Vena CavaLCRLocal Ca2+ ReleaseNCXNa+/Ca2+ exchangerPBSPhosphate-Buffered SalinepreBötCpreBötzinger ComplexROIRegion of InterestSANSinoatrial NodeSVCSuperior Vena CavaView Full Text

physiology↗