Title

Regulation of the gating of BKCa channel by lipid bilayer thickness

UMMS Affiliation

Department of Psychiatry, Brudnick Neuropsychiatric Research Institute

Date

1-9-2007

Document Type

Article

Subjects

Calcium; *Ion Channel Gating; Large-Conductance Calcium-Activated Potassium; Channels; Lipid Bilayers; Phosphatidylcholines; Phosphatidylethanolamines; Protein Conformation; Sphingomyelins

Disciplines

Biochemistry

Abstract

Transmembrane segments of ion channels tend to match the hydrophobic thickness of lipid bilayers to minimize mismatch energy and to maintain their proper organization and function. To probe how ion channels respond to mismatch with lipid bilayers of different thicknesses, we examined the single channel activities of BK(Ca) (hSlo alpha-subunit) channels in planar bilayers of binary mixtures of DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) with phosphatidylcholines (PCs) of varying chain lengths, including PC 14:1, PC 18:1, PC 22:1, PC 24:1, and with porcine brain sphingomyelin. Bilayer thickness and structure was measured with small angle x-ray diffraction and atomic force microscopy. The open probability (P(o)) of the BK(Ca) channel was finely tuned by bilayer thickness, first decreasing with increases in bilayer thickness from PC 14:1 to PC 22:1 and then increasing from PC 22:1 to PC 24:1 and to porcine brain sphingomyelin. Single channel kinetic analyses revealed that the mean open time of the channel increased monotonically with bilayer thickness and, therefore, could not account for the biphasic changes in P(o). The mean closed time increased with bilayer thickness from PC 14:1 up to PC 22:1 and then decreased with further increases in bilayer thickness to PC 24:1 and sphingomyelin, correlating with changes in P(o). This is consistent with the proposition that bilayer thickness affects channel activity mainly through altering the stability of the closed state. We suggest a simple mechanical model that combines forces of lateral stress within the lipid bilayer with local hydrophobic mismatch between lipids and the protein to account for the biphasic modulation of BK(Ca) gating.

Rights and Permissions

Citation: J Biol Chem. 2007 Mar 9;282(10):7276-86. Epub 2007 Jan 5. Link to article on publisher's site

DOI of Published Version

10.1074/jbc.M607593200

Related Resources

Link to Article in PubMed

Journal Title

The Journal of biological chemistry

PubMed ID

17209047