Title

Site of action of fatty acids and other charged lipids on BKCa channels from arterial smooth muscle cells

UMMS Affiliation

Department of Physiology

Date

11-1-2002

Document Type

Article

Subjects

Amines; Anions; Arteries; Cell Membrane; Cells, Cultured; Dose-Response Relationship, Drug; Fatty Acids; *Lipid Metabolism; Lipids; Membrane Potentials; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Palmitoyl Coenzyme A; Peptide Fragments; Potassium Channels, Calcium-Activated; Quaternary Ammonium Compounds; Trimethyl Ammonium Compounds

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Fatty acids and other negatively charged single-chain lipids increase large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel activity, whereas sphingosine and other positively charged single-chain lipids suppress activity. Because these molecules are effective on both inside-out and outside-out patches and because they can flip across the bilayer, the location of their site of action is unclear. To identify the site of action of charged lipids on this channel, we used two compounds that are unlikely to flip across the lipid bilayer. Palmitoyl coenzyme A (PCoA) was used to identify the site of action of negatively charged lipids, and a positively charged myristoylated pentapeptide (myr-KPRPK) was used to investigate the site of action of positively charged lipids. The effect of these compounds on channel activity was studied in excised patches using patch-clamp techniques. In "normal" ionic strength solutions and in experiments where high-ionic strength solutions were used to shield membrane surface charge, PCoA increased channel activity only when applied to outside-out patches, suggesting that the site of action of negatively charged lipids is located on the outer surface of the membrane. A decrease in activity, similar to that of other positively charged lipids, was observed only when myr-KPRPK was applied to outside-out patches, suggesting that positively charged lipids suppress activity by also acting on the outer membrane surface. Some channel blockade effects of myr-KPRPK and KPRPK are also described. The sidedness of action suggests that modulation of channel activity by single-chain lipids can occur by their interaction with the channel protein.

Rights and Permissions

Citation: Am J Physiol Cell Physiol. 2003 Mar;284(3):C607-19. Epub 2002 Oct 30. Link to article on publisher's site

DOI of Published Version

10.1152/ajpcell.00364.2002

Related Resources

Link to article in PubMed

Journal Title

American journal of physiology. Cell physiology

PubMed ID

12409285