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This Article Full Text Full Text (PDF) All Versions of this Article: 294/6/C1499    most recent 00365.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Smani, T. Articles by Bolotina, V. M. PubMed PubMed Citation Articles by Smani, T. Articles by Bolotina, V. M.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Complex regulation of store-operated Ca²⁺ entry pathway by PKC- in vascular SMCs

¹Ion Channel and Calcium Signaling Unit, Boston University School of Medicine, Boston, Massachusetts; and ²Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen de Roció/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla/Laboratorio de Investigación Cardiovascular, Sevilla, Spain

Submitted 15 August 2007 ; accepted in final form 16 April 2008

The role of PKC in the regulation of store-operated Ca²⁺ entry (SOCE) is rather controversial. Here, we used Ca²⁺-imaging, biochemical, pharmacological, and molecular techniques to test if Ca²⁺-independent PLA₂β (iPLA₂β), one of the transducers of the signal from depleted stores to plasma membrane channels, may be a target for the complex regulation of SOCE by PKC and diacylglycerol (DAG) in rabbit aortic smooth muscle cells (SMCs). We found that the inhibition of PKC with chelerythrine resulted in significant inhibition of thapsigargin (TG)-induced SOCE in proliferating SMCs. Activation of PKC by the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol (OAG) caused a significant depletion of intracellular Ca²⁺ stores and triggered Ca²⁺ influx that was similar to TG-induced SOCE. OAG and TG both produced a PKC-dependent activation of iPLA₂β and Ca²⁺ entry that were absent in SMCs in which iPLA₂β was inhibited by a specific chiral enantiomer of bromoenol lactone (S-BEL). Moreover, we found that PKC regulates TG- and OAG-induced Ca²⁺ entry only in proliferating SMCs, which correlates with the expression of the specific PKC- isoform. Molecular downregulation of PKC- impaired TG- and OAG-induced Ca²⁺ influx in proliferating SMCs but had no effect in confluent SMCs. Our results demonstrate that DAG (or OAG) can affect SOCE via multiple mechanisms, which may involve the depletion of Ca²⁺ stores as well as direct PKC--dependent activation of iPLA₂β, resulting in a complex regulation of SOCE in proliferating and confluent SMCs.

protein kinase C-; Ca²⁺-independent phospholipase A₂; diacylglycerol; smooth muscle cells