title: Less is more: minimal expression of myoendothelial gap junctions optimizes cell-cell communication in virtual arterioles.
abstract: Dysfunctional electrical signalling within the arteriolar wall is a major cause of cardiovascular disease. The endothelial cell layer constitutes the primary electrical pathway, co-ordinating contraction of the overlying smooth muscle cell (SMC) layer. As myoendothelial gap junctions (MEGJs) provide direct contact between the cell layers, proper vasomotor responses are thought to depend on a high, uniform MEGJ density. However, MEGJs are observed to be expressed heterogeneously within and among vascular beds. This discrepancy is addressed in the present study. As no direct measures of MEGJ conductance exist, we employed a computational modelling approach to vary the number, conductance and distribution of MEGJs. Our simulations demonstrate that a minimal number of randomly distributed MEGJs augment arteriolar cell-cell communication by increasing conduction efficiency and ensuring appropriate membrane potential responses in SMCs. We show that electrical coupling between SMCs must be tailored to the particular MEGJ distribution. Finally, observation of non-decaying mechanical conduction in arterioles without regeneration has been a long-standing controversy in the microvascular field. As heterogeneous MEGJ distributions provide for different conduction profiles along the cell layers, we demonstrate that a non-decaying conduction profile is possible in the SMC layer of a vessel with passive electrical properties. These intriguing findings redefine the concept of efficient electrical communication in the microcirculation, illustrating how heterogeneous properties, ubiquitous in biological systems, may have a profound impact on system behaviour and how acute local and global flow control is explained from the biophysical foundations.
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, Denmark bohald@sund.ku.dk.
authors.forename: Bjørn Olav
authors.initials: BO
authors.lastname: Hald
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, Denmark.
authors.forename: Jens Christian Brings
authors.initials: JC
authors.lastname: Jacobsen
authors.affiliation: Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Sippy Downs, Queensland, Australia Department of Physiology, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Shaun L
authors.initials: SL
authors.lastname: Sandow
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, Denmark.
authors.forename: Niels-Henrik
authors.initials: NH
authors.lastname: Holstein-Rathlou
authors.affiliation: Department of Physiology & Pharmacology, University of Calgary, Alberta, Canada.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Welsh
mesh_terms: D000818:Animals; D001160:Arterioles / Q000166:cytology / Q000502:physiology*; D002450:Cell Communication; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D017629:Gap Junctions / Q000378:metabolism / Q000502:physiology*; D008564:Membrane Potentials; D008955:Models, Cardiovascular; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology*; D051381:Rats
chemical_list: D017630:Connexins