Neurovascular coupling and the influence of luminal agonists via the endothelium

K. Dormanns, E.M.J. van Disseldorp, R.G. Brown, T. David

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)

Abstract

A numerical model of neurovascular coupling (NVC) is presented based on neuronal activity coupled to vasodilation/contraction models via the astrocytic mediated perivascular K+ and the smooth muscle cell Ca2+ pathway. Luminal agonists acting on P2Y receptors on the endothelial cell surface provide a flux of IP3 into the endothelial cytosol. This concentration of IP3 is transported via gap junctions between endothelial and smooth muscle cells providing a source of sacroplasmic derived Ca2+ in the smooth muscle cell. The model is able to relate a neuronal input signal to the corresponding vessel reaction. Results indicate that blood flow mediated IP3 production via the agonist ATP has a substantial effect on the contraction/dilation dynamics of the SMC. The resulting variation in cytosolic Ca2+ can enhance and inhibit the flow of blood to the cortical tissue. IP3 coupling between endothelial and smooth muscle cells seems to be important in the dynamics of the smooth muscle cell. The VOCC channels are, due to the hyperpolarisation from K+ SMC efflux, almost entirely closed and do not seem to play a significant role during neuronal activity. The current model shows that astrocytic Ca2+ is not necessary for neurovascular coupling to occur in contrast to a number of experiments outlining the importance of astrocytic Ca2+ in NVC, however this Ca2+ pathway is not the only one mediating NVC. Importantly agonists in flowing blood have a significant influence on the endothelial and smooth muscle cell dynamics.

Original languageEnglish
Pages (from-to)49-70
Number of pages22
JournalJournal of Theoretical Biology
Volume364
DOIs
Publication statusPublished - 7 Jan 2015

Keywords

  • Astrocyte
  • Mathematical modelling
  • Vasomotion

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