title: Gap junctions suppress electrical but not [Ca(2+)] heterogeneity in resistance arteries.
abstract: Despite stochastic variation in the molecular composition and morphology of individual smooth muscle and endothelial cells, the membrane potential along intact microvessels is remarkably uniform. This is crucial for coordinated vasomotor responses. To investigate how this electrical homogeneity arises, a virtual arteriole was developed that introduces variation in the activities of ion-transport proteins between cells. By varying the level of heterogeneity and subpopulations of gap junctions (GJs), the resulting simulations shows that GJs suppress electrical variation but can only reduce cytosolic [Ca(2+)] variation. The process of electrical smoothing, however, introduces an energetic cost due to permanent currents, one which is proportional to the level of heterogeneity. This cost is particularly large when electrochemically different endothelial-cell and smooth-muscle-cell layers are coupled. Collectively, we show that homocellular GJs in a passively open state are crucial for electrical uniformity within the given cell layer, but homogenization may be limited by biophysical or energetic constraints. Owing to the ubiquitous presence of ion transport-proteins and cell-cell heterogeneity in biological tissues, these findings generalize across most biological fields.
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: bohald@sund.ku.dk.
authors.forename: Bjørn Olav
authors.initials: BO
authors.lastname: Hald
authors.affiliation: Department of Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Welsh
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Niels-Henrik
authors.initials: NH
authors.lastname: Holstein-Rathlou
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens Chr Brings
authors.initials: JC
authors.lastname: Jacobsen
mesh_terms: D000818:Animals; D001160:Arterioles / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism; D055724:Electrophysiological Phenomena; D004734:Energy Metabolism; D017629:Gap Junctions / Q000378:metabolism*; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D051381:Rats
chemical_list: D017630:Connexins; D002118:Calcium