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- W2315754936 abstract "Pulmonary arterial smooth muscle cells (PASMC) are submitted to stretch forces exerted by the blood pressure. They can transduce a mechanical stimulus of stretch into a biological response of contraction, a mechanism called myogenic tone which involves Ca 2+ influx through stretch-activated channels (SAC). We investigate how the subcellular organization of Ca 2+ stores in PASMC (sarcoplasmic reticulum (SR), lysosomes and mitochondria) is important for the Ca 2+ response to stretch during PH. Studies were performed in freshly isolated PASMC from control rats and rats with a pulmonary hypertension induced by an injection of monocrotaline (MCT). Inward currents from SAC were recorded after a negative pressure applied by a patch-clamp pipette. Cytosolic Ca 2+ was also measured with the fluo4 probe and mitochondrial Ca 2+ with the rhod2 probe after an osmotic shock. A pharmacological approach coupled with different coimmunolabelings of ryanodine receptors (RyR) and SERCA2 pumps was used to investigate which RyR subtype is involved in Ca 2+ response to stretch. PASMC exhibit segregated Ca 2+ stores: a subplasmalemnal SR store with RyR1 and SERCA2b, associated to mitochondria and a perinuclear SR store with RyR3 and SERCA2a. We showed that a stretch of PASMC induces an inward Ca 2+ influx through SAC that is amplified by a Ca 2+ release by RyR1, which is buffered by mitochondria. In MCT rats, the subcellular organization of RyR subtypes is modified: RyR3 and SERCA2a are not only expressed in a perinuclear area but also in a subplasmalemnal level. This is correlated with a different organization of mitochondria. In MCT rats, this new organisation leads to a greater amplification by all RyR subtypes and to a higher Ca 2+ increase induced by stretch. Furthermore, the Ca 2+ response to stretch is enhanced by a mechanism independent on extracellular Ca 2+ , involving caveolae. The spatial organization of Ca 2+ stores in PASMC is important for cell signaling and plays a causal role in PH." @default.
- W2315754936 created "2016-06-24" @default.
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- W2315754936 date "2015-04-01" @default.
- W2315754936 modified "2023-09-26" @default.
- W2315754936 title "0169 : Segregated calcium stores are important for stretch-induced calcium signaling in smooth muscle cells: Implication in pulmonary hypertension" @default.
- W2315754936 doi "https://doi.org/10.1016/s1878-6480(15)30158-0" @default.
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