Modulation of BK(Ca) channel activity by fatty acids: structural requirements and mechanism of action
UMass Chan Affiliations
Department of PhysiologyDocument Type
Journal ArticlePublication Date
2002-10-10Keywords
AminesAnimals
Arachidonic Acid
Cell Membrane
Electrochemistry
Fatty Acids
Ion Channel Gating
Large-Conductance Calcium-Activated Potassium Channels
Muscle, Smooth, Vascular
Myristic Acid
Oleic Acid
Phosphoprotein Phosphatase
Potassium Channels, Calcium-Activated
Protein Kinases
Rabbits
Sphingosine
Structure-Activity Relationship
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
To determine the mechanism of fatty acid modulation of rabbit pulmonary artery large-conductance Ca2+ -activated K+ (BK(Ca)) channel activity, we studied effects of fatty acids and other lipids on channel activity in excised patches with patch-clamp techniques. The structural features of the fatty acid required to increase BK(Ca) channel activity (or average number of open channels, NP(o)) were identified to be the negatively charged head group and a sufficiently long (C > 8) carbon chain. Positively charged lipids like sphingosine, which have a sufficiently long alkyl chain (C >or= 8), produced a decrease in NP(o). Neutral and short-chain lipids did not alter NP(o). Screening of membrane surface charge with high-ionic-strength bathing solutions (330 mM K+ or 130 mM K+, 300 mM Na+) did not alter the modulation of the BK(Ca) channel NP(o) by fatty acids and other charged lipids, indicating that channel modulation is unlikely to be due to an alteration of the membrane electric field or the attraction of local counterions to the channel. Fatty acids and other negatively charged lipids were able to modulate BK(Ca) channel activity in bathing solutions containing 0 mM Ca2+, 20 mM EGTA, suggesting that calcium is not required for this modulation. Together, these results indicate that modulation of BK(Ca) channels by fatty acids and other charged lipids most likely occurs by their direct interaction with the channel protein itself or with some other channel-associated component.Source
Am J Physiol Cell Physiol. 2002 Nov;283(5):C1441-53. Link to article on publisher's site
DOI
10.1152/ajpcell.00035.2002Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38267PubMed ID
12372805Related Resources
ae974a485f413a2113503eed53cd6c53
10.1152/ajpcell.00035.2002