Biology subjects

Hernandez Mesa, M.

Publications and source records attributed to Hernandez Mesa, M..

2 recordsLinked to original sources

bioRxiv2023

Spine apparatus modulates Ca2+ in spines through spatial localization of sources and sinks

Dendritic spines are small protrusions on dendrites in neurons and serve as sites of postsynaptic activity. Some of these spines contain smooth endoplasmic reticulum (SER), and sometimes an even further specialized SER known as the spine apparatus (SA). In this work, we developed a stochastic spatial model to investigate the role of the SER and the SA in modulating Ca2+ dynamics. Using this model, we investigated how ryanodine receptor (RyR) localization, spine membrane geometry, and SER geometry can impact Ca2+ transients in the spine and in the dendrite. Our simulations found that RyR opening is dependent on where it is localized in the SER and on the SER geometry. In order to maximize Ca2+ in the dendrites (for activating clusters of spines and spine-spine communication), a laminar SA was favorable with RyRs localized in the neck region, closer to the dendrite. We also found that the presence of the SER without the laminar structure, coupled with RyR localization at the head, leads to higher Ca2+ presence in the spine. These predictions serve as design principles for understanding how spines with an ER can regulate Ca2+ dynamics differently from spines without ER through a combination of geometry and receptor localization. 1 HighlightsO_LIRyR opening in dendritic spine ER is location dependent and spine geometry dependent. C_LIO_LICa2+ buffers and SERCA can buffer against runaway potentiation of spines even when CICR is activated. C_LIO_LIRyRs located towards the ER neck allow for more Ca2+ to reach the dendrites. C_LIO_LIRyRs located towards the spine head are favorable for increased Ca2+ in spines. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=186 SRC="FIGDIR/small/558941v1_fig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1a2aa64org.highwire.dtl.DTLVardef@60a7c5org.highwire.dtl.DTLVardef@1a68303org.highwire.dtl.DTLVardef@e3743f_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1:C_FLOATNO Graphical abstract. Factors governing the dynamics of Ca2+ in dendritic spines include plasma membrane geometry, RyR distribution and ER laminarity. C_FIG

neuroscience↗

bioRxiv2021

Nanoscale organization of ryanodine receptor distribution and phosphorylation pattern determines the dynamics of calcium sparks

Super-resolution imaging techniques have provided a better understanding of the relationship between the nanoscale organization of function of ryanodine receptors (RyRs) in cardiomy-ocytes. Interestingly recent data have indicated that this relationship is disrupted in heart failure (HF), as RyRs are dispersed into smaller and more numerous clusters. However, RyRs are also hyperphosphorylated in this condition, and this is reported to occur preferentially within the cluster centre. Thus, the combined impact of RyR relocalization and sensitization on Ca2+ spark generation in failing cardiomyocytes is likely complex and these observations suggest that both the nanoscale organization of RyRs and the pattern of phosphorylated RyRs within clusters could be critical determinants of Ca2+ spark dynamics. To test this hypothesis, we used computational modeling to quantify the relationships between RyR cluster geometry, phosphorylation patterns, and sarcoplasmic reticulum (SR) Ca2+ release. We found that RyR cluster disruption results in a decrease in spark fidelity and longer sparks with a lower amplitude. Phosphorylation of some RyRs within the cluster can play a compensatory role, recovering healthy spark dynamics. Interestingly, our model predicts that such compensation is critically dependent on the phosphorylation pattern, as phosphorylation localized within the cluster center resulted in longer Ca2+ sparks and higher spark fidelity compared to a uniformly distributed phosphorylation pattern. Our results strongly suggest that both the phosphorylation pattern and nanoscale RyR reorganization are critical determinants of Ca2+ dynamics in HF. Significance StatementRyRs are ion channels located on the membrane of the sarcoplasmic reticulum that are responsible for an increase in cytosolic Ca2+ during cell excitation. Here, we investigate how the geometry of RyR clusters combined with spatial phosphorylation patterns impacts on Ca2+ spark generation and kinetics. The findings from our study show that both phosphorylation pattern and RyR cluster shape and dispersion have implications on Ca2+ spark activity and provide insights into altered Ca2+ dynamics during HF.

biophysics↗