Polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease (ADPKD), is a Ca2+-permeable nonselective cation channel

Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1182-7. doi: 10.1073/pnas.98.3.1182.


Defects in polycystin-2, a ubiquitous transmembrane glycoprotein of unknown function, is a major cause of autosomal dominant polycystic kidney disease (ADPKD), whose manifestation entails the development of fluid-filled cysts in target organs. Here, we demonstrate that polycystin-2 is present in term human syncytiotrophoblast, where it behaves as a nonselective cation channel. Lipid bilayer reconstitution of polycystin-2-positive human syncytiotrophoblast apical membranes displayed a nonselective cation channel with multiple subconductance states, and a high perm-selectivity to Ca2+. This channel was inhibited by anti-polycystin-2 antibody, Ca2+, La3+, Gd3+, and the diuretic amiloride. Channel function by polycystin-2 was confirmed by patch-clamping experiments of polycystin-2 heterologously infected Sf9 insect cells. Further, purified insect cell-derived recombinant polycystin-2 and in vitro translated human polycystin-2 had similar ion channel activity. The polycystin-2 channel may be associated with fluid accumulation and/or ion transport regulation in target epithelia, including placenta. Dysregulation of this channel provides a mechanism for the onset and progression of ADPKD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Calcium / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / genetics*
  • Calcium Channels / physiology
  • Cell Line
  • Cell Membrane / physiology
  • Female
  • Gadolinium / pharmacology
  • Humans
  • Lanthanum / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Proteins / drug effects
  • Membrane Proteins / genetics*
  • Membrane Proteins / physiology
  • Mutation*
  • Placenta / physiology
  • Polycystic Kidney, Autosomal Dominant / genetics*
  • Pregnancy
  • Protein Biosynthesis
  • Recombinant Proteins / drug effects
  • Recombinant Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spodoptera
  • TRPP Cation Channels
  • Transfection
  • Trophoblasts / physiology


  • Antibodies
  • Calcium Channels
  • Membrane Proteins
  • Recombinant Proteins
  • TRPP Cation Channels
  • polycystic kidney disease 2 protein
  • Lanthanum
  • Gadolinium
  • Calcium