title: Increases in endothelial Ca(2+) activate K(Ca) channels and elicit EDHF-type arteriolar dilation via gap junctions.
abstract: In skeletal muscle arterioles, the pathway leading to non-nitric oxide (NO), non-prostaglandin-mediated endothelium-derived hyperpolarizing factor (EDHF)-type dilations is not well characterized. To elucidate some of the steps in this process, simultaneous changes in endothelial intracellular Ca(2+) concentration ([Ca(2+)](i)) and the diameter of rat gracilis muscle arterioles (approximately 60 microm) to acetylcholine (ACh) were measured by fura 2 microfluorimetry (in the absence of NO and prostaglandins). ACh elicited rapid increases in endothelial [Ca(2+)](i) (101 +/- 7%), followed by substantial dilations (73 +/- 2%, coupling time: 1.3 +/- 0.2 s) that were prevented by endothelial loading of an intracellular Ca(2+) chelator [1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid]. Arteriolar dilations to ACh were also inhibited by intraluminal administration of the Ca(2+)-activated K(+) (K(Ca)) channel blockers charybdotoxin plus apamin or by palmitoleic acid, an uncoupler of myoendothelial gap junctions without affecting changes in endothelial [Ca(2+)](i). The presence of large conductance K(Ca) channels on arteriolar endothelial cells was demonstrated with immunohistochemisty. We propose that in skeletal muscle arterioles, EDHF-type mediation is evoked by an increase in endothelial [Ca(2+)](i), which by activating endothelial K(Ca) channels elicits hyperpolarization that is conducted via myoendothelial gap junctions to the smooth muscle resulting in decreases in [Ca(2+)](i) and consequently dilation.
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, New York 10595, USA.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Ungvari
authors.forename: Anna
authors.initials: A
authors.lastname: Csiszar
authors.forename: Akos
authors.initials: A
authors.lastname: Koller
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001160:Arterioles / Q000502:physiology* / Q000648:ultrastructure; D001685:Biological Factors / Q000502:physiology*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D004553:Electric Conductivity; D004730:Endothelium, Vascular / Q000737:chemistry / Q000378:metabolism*; D005456:Fluorescent Dyes; D016257:Fura-2; D017629:Gap Junctions / Q000502:physiology*; D007150:Immunohistochemistry; D018482:Muscle, Skeletal / Q000098:blood supply; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000378:metabolism; D009553:Nimodipine / Q000494:pharmacology; D015221:Potassium Channels / Q000032:analysis / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D001685:Biological Factors; D005456:Fluorescent Dyes; D015221:Potassium Channels; C067410:endothelium-dependent hyperpolarization factor; D018999:Charybdotoxin; D001030:Apamin; D009553:Nimodipine; D000109:Acetylcholine; D002118:Calcium; D016257:Fura-2