title: The mechanism of injury-induced intracellular calcium concentration oscillations in the endothelium of excised rat aorta.
abstract: Endothelial injury is the primary event that leads to a variety of severe vascular disorders. Mechanical injury elicits a Ca(2+) response in the endothelium of excised rat aorta, which comprises an initial Ca(2+) release from inositol-1,4,5-trisphosphate (InsP(3))-sensitive stores followed by a long-lasting decay phase due to Ca(2+) entry through uncoupled connexons. The Ca(2+) signal may also adopt an oscillatory pattern, the molecular underpinnings of which are unclear. In the light of the role played by Ca(2+) spiking in tissue regeneration, this study aimed to unveil the mechanisms underlying injury-induced Ca(2+) oscillations. The latter reversibly ceased upon removal of extracellular Ca(2+) or addition of the gap junction blockers heptanol, 18 α,β-glycyrrhetinic acid, La(3+) and Ni(2+), but were insensitive to BTP-2 and SKF 96365. The spiking response was abolished by inhibiting the Ca(2+) entry mode of the Na(+)/Ca(2+) exchanger (NCX). The InsP(3)-producing agonist ATP resumed Ca(2+) oscillations in silent cells, while the phospholipase C inhibitor U73122 suppressed them. Injury-induced Ca(2+) transients were prevented by the sarcoplasmic-endoplasmic reticulum calcium ATPase (SERCA) blockers thapsigargin and cyclopiazonic acid, while they were unaffected by suramin and genistein. These data show for the first time that the coordinated interplay between NCX-mediated Ca(2+) entry and InsP(3)-dependent Ca(2+) release contributes to injury-induced intracellular Ca(2+) concentration oscillations.
authors: Department of Biomedicine, School of Medicine, Benemérita Universidad Autónoma de Puebla, Puebla, México. rberra001@hotmail.com
authors: Roberto
authors: R
authors: Berra-Romani
authors: Abdul
authors: A
authors: Raqeeb
authors: Julián
authors: J
authors: Torres-Jácome
authors: Alejandro
authors: A
authors: Guzman-Silva
authors: Germano
authors: G
authors: Guerra
authors: Franco
authors: F
authors: Tanzi
authors: Francesco
authors: F
authors: Moccia
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D004730:Endothelium, Vascular / Q000293:injuries* / Q000378:metabolism; D017629:Gap Junctions / Q000502:physiology; D019850:Heptanol / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D058470:Receptors, Purinergic P2Y / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000502:physiology; D013830:Thiadiazoles / Q000494:pharmacology
chemical_list: C476308:4-methyl-4'-(3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl)-1,2,3-thiadiazole-5-carboxanilide; D000813:Anilides; D053496:Inositol 1,4,5-Trisphosphate Receptors; D058470:Receptors, Purinergic P2Y; D019831:Sodium-Calcium Exchanger; D013830:Thiadiazoles; D019850:Heptanol; D002118:Calcium