title: Protein kinases modulate store-operated channels in pulmonary artery smooth muscle cells.
abstract: BACKGROUND
  This study investigates whether protein kinase G (PKG), protein kinase A (PKA) and protein kinase C (PKC) are involved in the regulatory mechanisms of store-operated channel (SOC) in pulmonary arteries.
  
  
  METHODS
  Pulmonary artery smooth muscle cells (PASMCs) were enzymatically dissociated from rat intralobar pulmonary arteries. Whole cell, cell-attached and inside-out patch-clamp electrophysiology were used to monitor SOCs in isolated PASMCs.
  
  
  RESULTS
  Initially the Ca2+-ATPase inhibitor cyclopiazonic acid (CPA, 10 μM) initiated a whole cell current that was reduced by the SOC blocker SKF-96365 (10 μM). Subsequent work using both cell-attached and whole cell configurations revealed that the PKG and PKA inhibitors, KT5823 (3 μM) and H-89 (10 μM), also stimulated SOC activity; this augmentation was attenuated by the SOC blockers SKF-96365 (10 μM) and Ni2+ (0.1 mM). Finally using the inside-out configuration, the PKC activator phorbol 12-myristate 13-acetate (PMA, 10 μM) was confirmed to modestly stimulate SOC activity although this augmentation appeared to be more substantial following the application of 10 μM inositol 1,4,5-triphosphate (Ins(1,4,5)P3).
  
  
  CONCLUSIONS
  SOC activity in PASMCs was stimulated by the inhibition of PKG and PKA and the activation of PKC. Our findings suggest that the SOC could be a substrate of these protein kinases, which therefore would regulate the intracellular concentration of calcium and pulmonary arteriopathy via SOC.
authors.affiliation: Department of Pharmacology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: I-Shan
authors.initials: IS
authors.lastname: Chen
authors.forename: Zen-Kong
authors.initials: ZK
authors.lastname: Dai
authors.forename: Donald G
authors.initials: DG
authors.lastname: Welsh
authors.forename: Ing-Jun
authors.initials: IJ
authors.lastname: Chen
authors.forename: Bin-Nan
authors.initials: BN
authors.lastname: Wu
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D002118:Calcium