title: Non-linear relationship between hyperpolarisation and relaxation enables long distance propagation of vasodilatation.
abstract: Blood flow is adjusted to tissue demand through rapidly ascending vasodilatations resulting from conduction of hyperpolarisation through vascular gap junctions. We investigated how these dilatations can spread without attenuation if mediated by an electrical signal. Cremaster muscle arterioles were studied in vivo by simultaneously measuring membrane potential and vessel diameter. Focal application of acetylcholine elicited hyperpolarisations which decayed passively with distance from the local site,while dilatation spread upstream without attenuation. Analysis of simultaneous recordings at the local site revealed that hyperpolarisation and dilatation were only linearly related over a restricted voltage range to a threshold potential, beyond which dilatation was maximal. Experimental data could be simulated in a computational model with electrotonic decay of hyperpolarisation but imposition of this threshold. The model was tested by reducing the amplitude of the local hyperpolarisation which led to entry into the linear range closer to the local site and decay of dilatation. Serial section electron microscopy and light dye treatment confirmed that the spread of dilatation occurred through the endothelium and that the two cell layers were tightly coupled. Generality of the mechanism was demonstrated by applying the model to the attenuated propagation of dilatation found in larger arteries.We conclude that long distance spread of locally initiated dilatations is not due to a regenerative electrical phenomenon, but rather a restricted linear relationship between voltage and vessel tone, which minimises the impact of electrotonic decay of voltage. Disease-related alterations in endothelial coupling or ion channel expression could therefore decrease the ability to adjust blood flow to meet metabolic demand.
authors.affiliation: John Curtin School of Medical Research, GPO Box 334, Australian National University, Canberra, ACT, 2601, Australia. stephanie.wolfle@anu.edu.au
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Wölfle
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Chaston
authors.forename: Kenichi
authors.initials: K
authors.lastname: Goto
authors.forename: Shaun L
authors.initials: SL
authors.lastname: Sandow
authors.forename: Frank R
authors.initials: FR
authors.lastname: Edwards
authors.forename: Caryl E
authors.initials: CE
authors.lastname: Hill
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D017629:Gap Junctions / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D017711:Nonlinear Dynamics; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D000109:Acetylcholine