Skin capillary endothelial cells form a network of spatiotemporally conserved Ca(2+) activity.
A, S., DG, G., C, M.M., F, X., D, S., JL, M., Z, L., U, R., D, M.A., & JJ, M. (2026). Skin capillary endothelial cells form a network of spatiotemporally conserved Ca(2+) activity.. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.2519708123
A S, DG G, C MM, F X, D S, JL M, et al. Skin capillary endothelial cells form a network of spatiotemporally conserved Ca(2+) activity.. Proceedings of the National Academy of Sciences of the United States of America. 2026; doi: 10.1073/pnas.2519708123
A S, DG G, C MM, et al. Skin capillary endothelial cells form a network of spatiotemporally conserved Ca(2+) activity.[J]. Proceedings of the National Academy of Sciences of the United States of America. 2026. DOI: 10.1073/pnas.2519708123.
@article{a2026,
author = {Swaminathan A and Gonzalez DG and Matte-Martone C and Xu F and Simpson D and Moore JL and Lin Z and Rana U and Monedero-Alonso D and Mack JJ},
title = {Skin capillary endothelial cells form a network of spatiotemporally conserved Ca(2+) activity.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
doi = {10.1073/pnas.2519708123},
note = {PMID: 42335226},
}
TY - JOUR AU - Swaminathan A AU - Gonzalez DG AU - Matte-Martone C AU - Xu F AU - Simpson D AU - Moore JL AU - Lin Z AU - Rana U AU - Monedero-Alonso D AU - Mack JJ TI - Skin capillary endothelial cells form a network of spatiotemporally conserved Ca(2+) activity. T2 - Proceedings of the National Academy of Sciences of the United States of America PY - 2026 DO - 10.1073/pnas.2519708123 AN - PMID:42335226 ER -
Ca2+ signaling and its regulation are important for endothelial cell (EC) function and signaling. Yet, the spatiotemporal organization of Ca2+ activity and its regulation across a vascular plexus is poorly understood in an in vivo mammalian context. To overcome this gap in knowledge, we developed an intravital imaging approach to resolve Ca2+ activity with single-cell resolution in skin vasculature of adult mice via multiphoton microscopy. Here, we tracked thousands of Ca2+ events in the skin capillary plexus during homeostasis and observed signaling heterogeneity between ECs, with just over half displaying Ca2+ activity at any given time. Longitudinal tracking of the same mice revealed that the same capillary ECs maintain Ca2+ activity over days to weeks. Interestingly, activity dynamics, such as frequency and event duration, are not conserved at a single-cell level but are maintained at an EC population level. Molecularly, conditional deletion of the gap junction protein Connexin 43 (Cx43cKO) in ECs leads to a subset of ECs displaying sustained Ca2+ activity, biasing signaling dynamics of the whole network toward chronically persistent activity over time. Sustained capillary Ca2+ activity results in vascular permeability and flow dysregulation. Last, through pharmacological targeting of known agonists/antagonists, we showed that inhibition of L-type Voltage Gated Ca2+ channels non-cell-autonomously restores Ca2+ activity, blood flow, and barrier function in Cx43cKO mice. Collectively, our work provides insight into the spatial and temporal characteristics, extent, and regulation of Ca2+ activity in skin capillaries of live mice.