Lipid modulation of ion channels through specific binding sites

• Published in: Biochimica et biophysica acta Vol. 1838; no. 6; pp. 1560 - 1567
• Main Authors: Poveda, J.A., Giudici, A.M., Renart, M.L., Molina, M.L., Montoya, E., Fernández-Carvajal, A., Fernández-Ballester, G., Encinar, J.A., González-Ros, J.M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-06-2014
• Subjects: Annular and Non-annular lipid; Binding Sites; Ion channel; Ions - metabolism; KcsA; Lipid Bilayers - metabolism; Lipid modulation; Lipid–protein interaction; Membrane Lipids - metabolism; Potassium Channels - metabolism; Protein–protein interaction; Streptomyces lividans - metabolism; IP3R; KcsA; BK; RyR; ENaC; Kv; Lipid modulation; CRAC; Protein–protein interaction; GABAA; TRP; nAChR; FRET; Lipid–protein interaction; TRPL; hERG; BN-PAGE; HOP; TMD; MscL; LOP; Ion channel; Annular and Non-annular lipid; KATP; PA; SUR; CTD; HCN; PC; Kir; PG; KCNQ; VDAC; Cav; GIRK; PUFAs; CNG; PIP2
• ISSN: 0005-2736; 0006-3002; 1879-2642
• DOI: 10.1016/j.bbamem.2013.10.023

Ion channel conformational changes within the lipid membrane are a key requirement to control ion passage. Thus, it seems reasonable to assume that lipid composition should modulate ion channel function. There is increasing evidence that this implicates not just an indirect consequence of the lipid influence on the physical properties of the membrane, but also specific binding of selected lipids to certain protein domains. The result is that channel function and its consequences on excitability, contractility, intracellular signaling or any other process mediated by such channel proteins, could be subjected to modulation by membrane lipids. From this it follows that development, age, diet or diseases that alter lipid composition should also have an influence on those cellular properties. The wealth of data on the non-annular lipid binding sites in potassium channel from Streptomyces lividans (KcsA) makes this protein a good model to study the modulation of ion channel structure and function by lipids. The fact that this protein is able to assemble into clusters through the same non-annular sites, resulting in large changes in channel activity, makes these sites even more interesting as a potential target to develop lead compounds able to disrupt such interactions and hopefully, to modulate ion channel function. This Article is Part of a Special Issue Entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy.
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•Specific lipids bound to ion channels modulate their structure and function.•Non-annular lipid binding sites on KcsA mediate interactions leading to protein clustering.•Lipid–protein and protein–protein interactions strongly modulate KcsA function.