J. Abi Char and A. Maguy are to be regarded as joint first authors of this paper.
Membrane cholesterol modulates Kv1.5 potassium channel distribution and function in rat cardiomyocytes
Article first published online: 21 JUL 2007
The Journal of Physiology
Volume 582, Issue 3, pages 1205–1217, August 2007
How to Cite
Abi-Char, J., Maguy, A., Coulombe, A., Balse, E., Ratajczak, P., Samuel, J.-L., Nattel, S. and Hatem, S. N. (2007), Membrane cholesterol modulates Kv1.5 potassium channel distribution and function in rat cardiomyocytes. The Journal of Physiology, 582: 1205–1217. doi: 10.1113/jphysiol.2007.134809
- Issue published online: 21 JUL 2007
- Article first published online: 21 JUL 2007
- (Resubmitted 18 April 2007; accepted after revision 18 May 2007; first published online 24 May 2007)
Membrane lipid composition is a major determinant of cell excitability. In this study, we assessed the role of membrane cholesterol composition in the distribution and function of Kv1.5-based channels in rat cardiac membranes. In isolated rat atrial myocytes, the application of methyl-β-cyclodextrin (MCD), an agent that depletes membrane cholesterol, caused a delayed increase in the Kv1.5-based sustained component, Ikur, which reached steady state in ∼7 min. This effect was prevented by preloading the MCD with cholesterol. MCD-increased current was inhibited by low 4-aminopyridine concentration. Neonatal rat cardiomyocytes transfected with Green Fluorescent Protein (GFP)-tagged Kv1.5 channels showed a large ultrarapid delayed-rectifier current (IKur), which was also stimulated by MCD. In atrial cryosections, Kv1.5 channels were mainly located at the intercalated disc, whereas caveolin-3 predominated at the cell periphery. A small portion of Kv1.5 floated in the low-density fractions of step sucrose-gradient preparations. In live neonatal cardiomyocytes, GFP-tagged Kv1.5 channels were predominantly organized in clusters at the basal plasma membrane. MCD caused reorganization of Kv1.5 subunits into larger clusters that redistributed throughout the plasma membrane. The MCD effect on clusters was sizable 7 min after its application. We conclude that Kv1.5 subunits are concentrated in cholesterol-enriched membrane microdomains distinct from caveolae, and that redistribution of Kv1.5 subunits by depletion of membrane cholesterol increases their current-carrying capacity.