Regulation of the Na+:Ca2+ exchanger by angiotensin II-PKC in mesangial cells from salt Resistant (R) and salt Sensitive (S) rats

Academic Article

Abstract

  • These studies were carried out to determine if there is a difference in Angiotensin II (Ang II)-protein kinase C (PKC) regulation of the Na :Ca exchanger in cultured mesangial cells from Dahl/Rapp S and R rats. R and S mesangial cells were grown on coverslips, serum starved, and loaded with fura 2 to measure cytosolic calcium concentration ([Ca ] ). Exchanger activity was assessed by measuring changes in [Ca ] ) after reducing extracellular Na (Na ) from 150 to 2 mM. This maneuver was specific for the exchanger since the effects of reducing Na or [Ca ] ) were inhibited by 24 hr pretreatment with 100 nM of antisense oligonucleotide against the N-terminus transmembrane domain. Either Ang II (10 nM) or PKC activation by 15 min treatment with 100 nM PMA significantly increased *[Ca ] ) in response to removal of Na in R but not S mesangial cells. Increase in exchanger activity by either PMA or Ang II was abolished by prior 24 hr exposure to PMA, a maneuver that downregulates PKC activity. In addition, immunofluorescence studies showed that PKC activation translocated the Na :Ca exchanger to the plasma membrane in R but not S mesangial cells. These data demonstrate that Ang II stimulates Na :Ca exchange activity via PKC in R mesangial cells. This process involves translocation of the exchanger from the cytoplasm to the plasma membrane and appears to be defective in S mesangial cells. + 2+ 2+ 2+ 2+ 2+ + 2+ + 2+ i i e e i i e
  • Published In

  • The FASEB Journal  Journal
  • Author List

  • Unlap MT; Isbell C; Bell PP
  • Volume

  • 12
  • Issue

  • 5