title: Stretch-induced Ca2+ signalling in vascular smooth muscle cells depends on Ca2+ store segregation.
abstract: OBJECTIVE
  Calcium is a key second messenger that can be mobilized from both the extracellular medium and intracellular calcium stores. Pulmonary arterial smooth muscle cells (PASMCs) respond to stretch by a calcium increase, a mechanism enhanced during pulmonary hypertension (PH). We investigated the role of the spatial organization between plasma membrane stretch-activated channels (SACs) and intracellular calcium stores [sarcoplasmic reticulum (SR), mitochondria, and lysosomes) in response to stretch.
  
  
  RESULTS
  Studies were performed in freshly isolated PASMCs from both control and two different rat models of PH (chronically hypoxic and monocrotaline-treated rats). Co-immunolabellings revealed that the subcellular segregation between each subtype of SR ryanodine receptors (RyR1, RyR2, and RyR3), SERCA2 pumps (SERCA2a and SERCA2b), mitochondria, or lysosomes in freshly isolated PASMCs differs from control and PH PASMCs. In control PASMCs, stretching the membrane activates a Ca(2+) influx through SACs. This influx is amplified by cell hyperpolarization, a calcium release by subplasmalemmal RyR1 and is then buffered by mitochondria. In two different PH rat models, the calcium response to stretch is enhanced due to hyper-reactivity of SACs and a greater calcium amplification by all RyR subtypes.
  
  
  CONCLUSIONS
  The spatial organization of RyR and calcium stores in PASMCs is important for cell signalling and plays a causal role in PH.
authors.affiliation: Centre de Recherche Cardio-Thoracique de Bordeaux, Universite de Bordeaux, Bordeaux F-33000, France Centre de Recherche Cardio-Thoracique de Bordeaux, INSERM, U 1045, Bordeaux F-33000, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Gilbert
authors.affiliation: Centre de Recherche Cardio-Thoracique de Bordeaux, Universite de Bordeaux, Bordeaux F-33000, France Centre de Recherche Cardio-Thoracique de Bordeaux, INSERM, U 1045, Bordeaux F-33000, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ducret
authors.affiliation: Centre de Recherche Cardio-Thoracique de Bordeaux, Universite de Bordeaux, Bordeaux F-33000, France Centre de Recherche Cardio-Thoracique de Bordeaux, INSERM, U 1045, Bordeaux F-33000, France CHU Bordeaux, Exploration Fonctionnelle Respiratoire, Bordeaux F-33000, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Marthan
authors.affiliation: Centre de Recherche Cardio-Thoracique de Bordeaux, Universite de Bordeaux, Bordeaux F-33000, France Centre de Recherche Cardio-Thoracique de Bordeaux, INSERM, U 1045, Bordeaux F-33000, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Savineau
authors.affiliation: Centre de Recherche Cardio-Thoracique de Bordeaux, Universite de Bordeaux, Bordeaux F-33000, France Centre de Recherche Cardio-Thoracique de Bordeaux, INSERM, U 1045, Bordeaux F-33000, France Centre de Recherche Cardio-Thoracique de Bordeaux, 146 rue Léo Saignat, Bat TP - 2ème étage, 33076 Bordeaux Cedex, France jean-francois.quignard@u-bordeaux.fr.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Quignard
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D006976:Hypertension, Pulmonary / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D011651:Pulmonary Artery / Q000378:metabolism; D011661:Pulmonary Stretch Receptors / Q000378:metabolism; D017208:Rats, Wistar; D012433:Ryanodine / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum
chemical_list: D002121:Calcium Channel Blockers; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D002118:Calcium
keywords: Calcium signalling; Osmotic shock; Pulmonary hypertension; Ryanodine receptor; Stretch-activated channel