Caveolin regulates kv1.5 trafficking to cholesterol-rich membrane microdomains

Mol Pharmacol. 2008 Mar;73(3):678-85. doi: 10.1124/mol.107.042093. Epub 2007 Nov 28.


The targeting of ion channels to cholesterol-rich membrane microdomains has emerged as a novel mechanism of ion channel localization. Previously, we reported that Kv1.5, a prominent cardiovascular K(+) channel alpha-subunit, localizes to caveolar microdomains. However, the mechanisms regulating Kv1.5 targeting and the functional significance of this localization are largely unknown. In this study, we demonstrate a role for caveolin in the trafficking of Kv1.5 to lipid raft microdomains where cholesterol modulates channel function. In cells lacking endogenous caveolin-1 or -3, the association of Kv1.5 with low-density, detergent-resistant membrane fractions requires coexpression with exogenous caveolin, which can form channel-caveolin complexes. Caveolin is not required for cell surface expression, however, and caveolin-trafficking mutants sequester Kv1.5, but not Kv2.1, in intracellular compartments, resulting in a loss of functional cell surface channel. Coexpression with wild type caveolin-1 does not alter Kv1.5 current density; rather, it induces depolarizing shifts in steady-state activation and inactivation. These shifts are analogous to those produced by elevation of membrane cholesterol. Together, these results show that caveolin modulates channel function by regulating trafficking to cholesterol-rich membrane microdomains.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caveolin 1 / chemistry
  • Caveolin 1 / genetics
  • Caveolin 1 / metabolism
  • Caveolin 3 / chemistry
  • Caveolin 3 / genetics
  • Caveolin 3 / metabolism
  • Caveolins / genetics
  • Caveolins / metabolism
  • Caveolins / physiology*
  • Cell Line
  • Cholesterol / metabolism
  • DNA, Complementary
  • Electrophysiology
  • Female
  • Immunohistochemistry
  • Kv1.5 Potassium Channel / metabolism*
  • Membrane Microdomains / chemistry*
  • Mutation
  • Patch-Clamp Techniques
  • Protein Transport
  • Rats
  • Recombinant Fusion Proteins / metabolism


  • Caveolin 1
  • Caveolin 3
  • Caveolins
  • DNA, Complementary
  • Kv1.5 Potassium Channel
  • Recombinant Fusion Proteins
  • Cholesterol