title: Communication of agonist-induced electrical responses along 'capillaries' in vitro can be modulated by lipopolysaccharide, but not nitric oxide.
abstract: Communication of agonist-induced membrane potential changes along blood vessels has been proposed to contribute to the coordination of microvascular function. Factors mediating septic shock may compromise this coordination. Using electrophysiology in a simplified in vitro model of endothelial cells grown as capillary-like structures, we aimed to determine (i) the effect of lipopolysaccharide (LPS) on endothelial cell membrane potential responses to ATP and KCl and (ii) the effect of LPS and nitric oxide (NO) on cell-to-cell communication. Treatment of 'capillaries' with LPS (10 microg/ml for 1 h) did not affect local responsiveness to ATP or KCl, but reduced cell communication by a tyrosine-kinase-dependent mechanism. Treatment of 'capillaries' with the NO donor DETA (100 microM) or the NO synthase inhibitor L-NAME (100 microM) had no effect on cell communication or the response to LPS. Endogenous NO production, stimulated by LPS + interferon-gamma (100 U/ml) treatment, also had no effect on cell communication beyond that of LPS alone. We conclude that LPS, but not NO, can modulate conduction of agonist-induced electrical responses along endothelial capillary-like structures in vitro.
authors.affiliation: Child Health Research Institute, University of Western Ontario, London, Ont., Canada.
authors.forename: Darcy
authors.initials: D
authors.lastname: Lidington
authors.forename: Yves
authors.initials: Y
authors.lastname: Ouellette
authors.forename: Karel
authors.initials: K
authors.lastname: Tyml
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002196:Capillaries / Q000166:cytology* / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D003671:DEET / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats
chemical_list: D008070:Lipopolysaccharides; D020030:Nitric Oxide Donors; D003671:DEET; D009569:Nitric Oxide; D011189:Potassium Chloride; D007371:Interferon-gamma; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D019331:NG-Nitroarginine Methyl Ester