title: Waves of calcium depletion in the sarcoplasmic reticulum of vascular smooth muscle cells: an inside view of spatiotemporal Ca2+ regulation.
abstract: Agonist-stimulated smooth muscle Ca2+ waves regulate blood vessel tone and vasomotion. Previous studies employing cytoplasmic Ca2+ indicators revealed that these Ca2+ waves were stimulated by a combination of inositol 1,4,5-trisphosphate- and Ca2+ -induced Ca2+ release from the endo/sarcoplasmic reticulum. Herein, we present the first report of endothelin-1 stimulated waves of Ca2+ depletion from the sarcoplasmic reticulum of vascular smooth muscle cells using a calsequestrin-targeted Ca2+ indicator. Our findings confirm that these waves are due to regenerative Ca2+ -induced Ca2+ release by the receptors for inositol 1,4,5-trisphosphate. Our main new finding is a transient elevation in SR luminal Ca2+ concentration ([Ca2+](SR)) both at the site of wave initiation, just before regenerative Ca2+ release commences, and at the advancing wave front, during propagation. This strongly suggests a role for [Ca2+](SR) in the activation of inositol 1,4,5-trisphosphate receptors during agonist-induced calcium waves. In addition, quantitative analysis of the gradual decrease in the velocity of the depletion wave, observed in the absence of external Ca2+, indicates continuity of the lumen of the sarcoplasmic reticulum network. Finally, our observation that the depletion wave was arrested by the nuclear envelope may have implications for selective Ca2+ signalling.
authors: Child & Family Research Institute, Department of Anaesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada. mesfandiarei@gmail.com
authors: Mitra
authors: M
authors: Esfandiarei
authors: Nicola
authors: N
authors: Fameli
authors: Yohan Y H
authors: YY
authors: Choi
authors: Arash Y
authors: AY
authors: Tehrani
authors: Jeremy G
authors: JG
authors: Hoskins
authors: Cornelis
authors: C
authors: van Breemen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002138:Calibration; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D019284:Thapsigargin; D002118:Calcium