Protein kinases modulate store-operated channels in pulmonary artery smooth muscle cells

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 m) initiated a whole cell current that was reduced by the soc blocker skf-96365 (10 m). subsequent work using both cell-attached and whole cell configurations revealed that the pkg and pka inhibitors,kt5823 (3 m) and h-89 (10 m),also stimulated soc activity; this augmentation was attenuated by the soc blockers skf-96365 (10 m) and ni2+ (0.1 mm). finally using the inside-out configuration,the pkc activator phorbol 12-myristate 13-acetate (pma,10 m) was confirmed to modestly stimulate soc activity although this augmentation appeared to be more substantial following the application of 10 m 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. © 2011 chen et al; licensee biomed central ltd.