Search bioRxiv⌕ Search

Biology subjects

Tagirova, S.

Publications and source records attributed to Tagirova, S..

2 recordsLinked to original sources

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↗

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

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 networks 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 AP firing rate in a cooperative manner. However, these heterogeneities reduce the effect of {beta}-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 {beta}-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.

biophysics↗