PubMed Health⌕ Search

PubMed · 11444952

Arrhythmia as a result of poor intercellular coupling in the sinus node: a simulation study.

Abstract

The effects of reduced intercellular coupling in the sinus node were investigated by means of simulations. Coupling was reduced both uniformly, and by introducing localized interaction blocks. In either case, model sinus node element networks typically splitted into frequency domains. These were defined as groups of neighbour elements which all attained the same mean firing frequency. In systems, simulating the vicinity of an impulse outlet to the atrium, the sinus node elements often splitted into two domains, one slowly firing just inside the outlet, and one normally firing large domain in the sinus node interior. This two-domain situation was analysed using a two-element system. Wenckebach conduction and advanced (m:1) exit blocks were seen, together with more odd block patterns and slow chaotic rhythms. The two-domain situation appeared also when two discrete outlets were considered. The slow domains around each outlet synchronized via the atrium. However, if there were some degree of exit block through one of the outlets only, brady-tachy like rhythms could be simulated due to a re-entrant circuit including both sinus node and atrial tissue. In conclusion, poor coupling in the sinus node seems to be sufficient to produce most arrhythmias in the sick sinus syndrome

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

P Ostborn, B Wohlfart, G Ohlén. 2001-08-07. Arrhythmia as a result of poor intercellular coupling in the sinus node: a simulation study.. https://doi.org/10.1006/jtbi.2001.2339

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Differential cell signaling testing for cell-cell communication inference from single-cell data by dominoSignal.

MOTIVATION: Algorithms for ligand-receptor network inference have emerged as commonly used tools to estimate cell-cell communication from reference single-cell data. Many studies employ these algorithms to compare signaling between conditions and lack methods to statistically identify signals that are significantly different. We previously developed the cell communication inference algorithm Domino, which considers ligand and receptor gene expression in association with downstream transcription factor activity scoring. We developed the dominoSignal software to innovate upon Domino and extend its functionality to test statistically differential cellular signaling. RESULTS: This new functionality includes the compilation of active signals as linkages from multiple subjects in a single-cell data set and testing condition-dependent signaling linkage. The software is applicable for analysis of single-cell data sets with multiple subjects as biological replicates as well as with bootstrapped replicates from data sets with few or pooled subjects. We use simulation studies to benchmark the number of subjects in compared groups and cells within an annotated cell type sufficient to accurately identify differential linkages. We demonstrate the application of the Differential Cell Signaling Test (DCST) in the dominoSignal software to investigate consequences of cancer cell phenotypes and immunotherapy on cell-cell communication in tumor microenvironments. These applications in cancer studies demonstrate the ability of differential cell signaling analysis to infer changes to cell communication networks from therapeutic or experimental perturbations, which is broadly applicable across biological systems. AVAILABILITY: dominoSignal is available through Bioconductor at https://www.bioconductor.org/packages/release/bioc/html/dominoSignal.html.

Cell Communication↗

ZAP-70 kinase regulates HIV cell-to-cell spread and virological synapse formation.

HIV efficiently spreads in lymphocytes, likely through virological synapses (VSs). These cell-cell junctions share some characteristics with immunological synapses, but cellular proteins required for their constitution remain poorly characterized. We have examined here the role of ZAP-70, a key kinase regulating T-cell activation and immunological synapse formation, in HIV replication. In lymphocytes deficient for ZAP-70, or expressing a kinase-dead mutant of the protein, HIV replication was strikingly delayed. We have characterized further this replication defect. ZAP-70 was dispensable for the early steps of viral cycle, from entry to expression of viral proteins. However, in the absence of ZAP-70, intracellular Gag localization was impaired. ZAP-70 was required in infected donor cells for efficient cell-to-cell HIV transmission to recipients and for formation of VSs. These results bring novel insights into the links that exist between T-cell activation and HIV spread, and suggest that HIV usurps components of the immunological synapse machinery to ensure its own spread through cell-to-cell contacts.

Cell Communication↗

Gap junctional intercellular communication capacity by gap-FRAP technique: a comparative study.

Gap junctions play an important role in vital functions, including the regulation of cell growth and cell differentiation. Connexins 43 (Cx43) are the most widely expressed gap junction proteins. Cellular localization of phosphorylated Cx43 has been implicated in the capacity of gap junctional intercellular communication (GJIC). To follow the functionality of GJIC of different cell types, in monolayer cultures, characterized by different patterns of phosphorylated Cx43, we used a fluorescence recovery after photobleaching (FRAP) technique, and compared two tracers, 5(6)-carboxyfluorescein diacetate (CFDA) and calcein acetoxymethylester (AM). The GJIC capacity was quantified by estimating fluorescence redistribution parameters. The functionality of GJIC was in relation with the staining localization of phosphorylated Cx43 to the cell-cell contact areas, corresponding to gap junctions between contacting cells. GJIC involvement in fluorescence restitution after photobleaching was checked by a gap junction channel inhibition assay. We demonstrated that the choice of the dye did not significantly influence the fluorescence recovery percentages despite a cell line-dependent CFDA release, whereas it had an important impact on fluorescence kinetic profiles. This study reinforces the interest of the gap-FRAP approach to quantify modifications in the functionality of gap junctions and, above all, argues about the limits of CFDA for 3-D future approaches.

Cell Communication↗