title: Chronic Hypoxia Increases Intracellular Ca(2+) Concentration via Enhanced Ca(2+) Entry Through Receptor-Operated Ca(2+) Channels in Pulmonary Venous Smooth Muscle Cells.
abstract: BACKGROUND
  Hypoxic pulmonary hypertension (HPH) is characterized by pulmonary vascular remodeling. Intracellular Ca(2+)concentration ([Ca(2+)]i) is an essential signal for myocyte proliferation. Whether chronic hypoxia (CH) affects the basal [Ca(2+)]I and Ca(2+)entry through store- and/or receptor-operated calcium channels (SOCC, ROCC), and whether canonical transient receptor potential (TRPC) proteins are involved in CH-induced Ca(2+)influx and proliferation in pulmonary venous smooth muscle cells (PVSMCs) is examined.
  
  
  RESULTS
  Rats were exposed to CH. PVSMCs were isolated from distal pulmonary veins. In freshly isolated PVSMCs, CH increased the basal [Ca(2+)]i; removal of Ca(2+)or application of SKF-96365 reversed the elevated [Ca(2+)]i, whereas nifedipine had no effect. Receptor-operated Ca(2+)entry (ROCE) was expressed in PVSMCs. In freshly isolated PVSMCs from CH rats, ROCE was enhanced, whereas store-operated Ca(2+)entry had no alteration. Furthermore, real-time polymerase chain reaction and western blotting showed that mRNA and protein expression level of TRPC6, but neither TRPC1 nor TRPC3, in pulmonary venous smooth muscle (PV) from CH rats and PVSMCs exposed to CH was greater than in normal PV and PVSMCs. The knockdown of TRPC6 in hypoxic PVSMCs with siRNA inhibited the enhanced ROCE and attenuated CH-induced PVSMCs proliferation.
  
  
  CONCLUSIONS
  The enhanced Ca(2+)entry through ROCC, due to upregulated TRPC6, is a novel pathogenic mechanism contributing to the increased basal [Ca(2+)]iin PVSMCs and excessive PVSMC proliferation during the development of HPH.
authors.affiliation: Guangzhou Institute of Respiratory Disease, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University.
authors.forename: Gongyong
authors.initials: G
authors.lastname: Peng
authors.forename: Shaoxing
authors.initials: S
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Hong
authors.forename: Jinxing
authors.initials: J
authors.lastname: Hu
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Jiang
authors.forename: Guoping
authors.initials: G
authors.lastname: Hu
authors.forename: Yimin
authors.initials: Y
authors.lastname: Zou
authors.forename: Yumin
authors.initials: Y
authors.lastname: Zhou
authors.forename: Juan
authors.initials: J
authors.lastname: Xu
authors.forename: Pixin
authors.initials: P
authors.lastname: Ran
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling; D002908:Chronic Disease; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D011667:Pulmonary Veins / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D050051:Transient Receptor Potential Channels / Q000378:metabolism*; D066253:Vascular Remodeling
chemical_list: D015220:Calcium Channels; D050051:Transient Receptor Potential Channels; D002118:Calcium