Background K(2P) channels KCNK3/9/15 limit the budding of cell membrane-derived vesicles

Cell Biochem Biophys. 2011 Dec;61(3):585-94. doi: 10.1007/s12013-011-9241-1.


The main function of background two-pore potassium (K(2P)) channels KCNK3/9/15 is to stabilize the cell membrane potential. We previously observed that membrane potential depolarization enhances the release of HIV-1 viruses. Because membrane polarization affects the biomembrane directly, here we examined the effects of KCNK3/9/15 on the budding of nonviral vesicles. We found that depolarization by knocking down endogenous KCNK3/9/15 promoted secretion of cell-derived vesicles. We further used Vpu (an antagonist of KCNK3) as a model for the in vivo study of depolarization-stimulated secretion. Vpu is a HIV-1-encoded, ion channel-like protein (viroporin) capable of enhancing virus release and depolarizing the cell membrane potential. We found that Vpu could also promote nonviral vesicle release, perhaps through a similar mechanism that Vpu utilizes to promote viral particle release. Notably, T cells expressing Vpu alone became pathologically low in intracellular K(+) and insensitive to extracellular K(+) or membrane potential stimulation. In contrast, heterologous expression of KCNK3 in T cells stabilized the cell potentials by maintaining intracellular K(+). We thus concluded that KCNK3/9/15 expression limits membrane depolarization and depolarization-induced secretion at least in part by maintaining intracellular K(+).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism*
  • Cell Membrane / virology
  • Diphenylhexatriene / analogs & derivatives
  • Diphenylhexatriene / metabolism
  • Exocytosis / drug effects
  • HIV-1 / physiology
  • HeLa Cells
  • Human Immunodeficiency Virus Proteins / pharmacology
  • Humans
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Intracellular Space / virology
  • K562 Cells
  • Membrane Potentials / drug effects
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / metabolism
  • Potassium / metabolism
  • Potassium Channels, Tandem Pore Domain / antagonists & inhibitors
  • Potassium Channels, Tandem Pore Domain / metabolism*


  • Human Immunodeficiency Virus Proteins
  • KCNK15 protein, human
  • KCNK9 protein, human
  • Nerve Tissue Proteins
  • Potassium Channels, Tandem Pore Domain
  • Diphenylhexatriene
  • potassium channel subfamily K member 3
  • 1-(4-(trimethylamino)phenyl)-6-phenylhexa-1,3,5-triene
  • Potassium