PMID- 24692174 OWN - NLM STAT- MEDLINE DCOM- 20150526 LR - 20140714 IS - 1755-3245 (Electronic) IS - 0008-6363 (Linking) VI - 103 IP - 2 DP - 2014 Jul 15 TI - Stretch-induced Ca2+ signalling in vascular smooth muscle cells depends on Ca2+ store segregation. PG - 313-23 LID - 10.1093/cvr/cvu069 [doi] AB - AIM: 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. METHODS AND 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. CONCLUSION: The spatial organization of RyR and calcium stores in PASMCs is important for cell signalling and plays a causal role in PH. CI - Published on behalf of the European Society of Cardiology. All rights reserved. (c) The Author 2014. For permissions please email: journals.permissions@oup.com. FAU - Gilbert, Guillaume AU - Gilbert G AD - 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. FAU - Ducret, Thomas AU - Ducret T AD - 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. FAU - Marthan, Roger AU - Marthan R AD - 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. FAU - Savineau, Jean-Pierre AU - Savineau JP AD - 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. FAU - Quignard, Jean-Francois AU - Quignard JF AD - 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 Leo Saignat, Bat TP - 2eme etage, 33076 Bordeaux Cedex, France jean-francois.quignard@u-bordeaux.fr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140401 PL - England TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Calcium Channel Blockers) RN - 0 (Ryanodine Receptor Calcium Release Channel) RN - 15662-33-6 (Ryanodine) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Calcium/*metabolism MH - Calcium Channel Blockers/pharmacology MH - Calcium Signaling/drug effects/*physiology MH - Hypertension, Pulmonary/metabolism MH - Male MH - Muscle, Smooth, Vascular/drug effects/*metabolism MH - Myocytes, Smooth Muscle/drug effects/*metabolism MH - Pulmonary Artery/metabolism MH - Pulmonary Stretch Receptors/metabolism MH - Rats, Wistar MH - Ryanodine/metabolism MH - Ryanodine Receptor Calcium Release Channel/metabolism MH - Sarcoplasmic Reticulum OTO - NOTNLM OT - Calcium signalling OT - Osmotic shock OT - Pulmonary hypertension OT - Ryanodine receptor OT - Stretch-activated channel EDAT- 2014/04/03 06:00 MHDA- 2015/05/27 06:00 CRDT- 2014/04/03 06:00 PHST- 2014/04/03 06:00 [entrez] PHST- 2014/04/03 06:00 [pubmed] PHST- 2015/05/27 06:00 [medline] AID - cvu069 [pii] AID - 10.1093/cvr/cvu069 [doi] PST - ppublish SO - Cardiovasc Res. 2014 Jul 15;103(2):313-23. doi: 10.1093/cvr/cvu069. Epub 2014 Apr 1.