Inhibition of calcineurin phosphatase promotes exocytosis of renin from juxtaglomerular cells

Kidney Int. 2010 Jan;77(2):110-7. doi: 10.1038/ki.2009.418. Epub 2009 Nov 11.


To examine the role of the calcium/calmodulin-dependent phosphatase calcineurin in regulation of renin release, we assayed exocytosis using whole-cell patch clamp of single juxtaglomerular cells in culture. The calcineurin inhibitor, cyclosporine A (CsA), significantly increased juxtaglomerular cell membrane capacitance, an index of cell surface area and an established measure of exocytosis in single-cell assays. This effect was mimicked by intracellular delivery of a calcineurin inhibitory peptide, the calcium chelator ethylene glycol tetraacetic acid (EGTA), or the calmodulin inhibitor W-13. Simultaneous exposure to EGTA and CsA had no additive effect. The protein kinase A (PKA) blocker RpcAMPs had no effect on the CsA-induced increase in membrane capacitance. Intra- and extracellular application of tacrolimus did not alter membrane capacitance. A calmodulin antagonist (calmidazolium) and CsA, but not tacrolimus, significantly stimulated renin release from cultured juxtaglomerular cells. Juxtaglomerular cells expressed the calcineurin isoforms A-beta and A-gamma but not A-alpha. Plasma renin concentrations (PRCs) were not different in wild-type, calcineurin A-alpha, or A-beta knockout mice but increased after CsA treatment of the A-alpha knockout, while renin mRNA was suppressed. We conclude that calcineurin and calcium/calmodulin suppress exocytosis of renin from juxtaglomerular cells independent of PKA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcineurin / genetics
  • Calcineurin / metabolism*
  • Calcium / antagonists & inhibitors
  • Calcium / metabolism*
  • Calmodulin / antagonists & inhibitors
  • Cells, Cultured
  • Chelating Agents
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclosporine
  • Egtazic Acid
  • Electric Capacitance
  • Exocytosis*
  • Immunosuppressive Agents
  • Juxtaglomerular Apparatus / metabolism*
  • Male
  • Mice
  • Patch-Clamp Techniques
  • Phosphoric Monoester Hydrolases / antagonists & inhibitors
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Renin / blood
  • Renin / metabolism*
  • Sulfonamides


  • Calmodulin
  • Chelating Agents
  • Immunosuppressive Agents
  • Protein Isoforms
  • RNA, Messenger
  • Sulfonamides
  • Egtazic Acid
  • N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide
  • Cyclosporine
  • Cyclic AMP-Dependent Protein Kinases
  • calcineurin phosphatase
  • Calcineurin
  • Phosphoric Monoester Hydrolases
  • Renin
  • Calcium