QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: mol.105.012971v1 68/1/4    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Crowley, J. J. Articles by Dopico, A. M. Search for Related Content PubMed PubMed Citation Articles by Crowley, J. J. Articles by Dopico, A. M.

ACCELERATED COMMUNICATION

Distinct Structural Features of Phospholipids Differentially Determine Ethanol Sensitivity and Basal Function of BK Channels

Program in Neuroscience, Departments of Neurobiology (J.J.C., S.N.T.) and Psychiatry (S.N.T.), and Brudnick Neuropsychiatric Research Institute (S.N.T.), University of Massachusetts Medical School, Worcester, Massachusetts; and Department of Pharmacology, the University of Tennessee Health Science Center, Memphis, Tennessee (A.M.D.)

Large conductance Ca²⁺-activated K⁺ (BK) channel activity and its potentiation by ethanol are both critically modulated by bilayer phosphatidylserine (PS), a phospholipid involved in membrane-bound signaling. Whether PS is uniquely required for ethanol to modify channel activity is unknown. Furthermore, the structural determinants in membrane phospholipid molecules that control alcohol action remain to be elucidated. We addressed these questions by reconstituting BK channels from human brain (hslo) into bilayers that contained phospholipids differing in headgroup size, charge, and acyl chain saturation. Data demonstrate that ethanol potentiation of hslo channels is blunted by conical phospholipids but favored by cylindrical phospholipids, independently of phospholipid charge. As found with ethanol action, basal channel activity is higher in bilayers containing cylindrical phospholipids. Basal activity and its ethanol potentiation in bilayers containing phosphatidylcholine, however, are not as robust as in those containing PS. These results are best interpreted as resulting from the relief of bilayer stress caused by inclusion of cylindrical phospholipids, with this relief being synergistically evoked by molecular shape and negative headgroup charge. Present findings suggest that hslo gating structures targeted by ethanol are accessible to sense changes in bilayer stress. In contrast, hslo unitary conductance is significantly higher in bilayers that contain negatively charged phospholipids independently of molecular shape, a result that is likely to be dependent on an interaction between anionic phospholipids and deep channel residues coupled to the selectivity filter.

This article has been cited by other articles:

				C. Yuan, R. J. O'Connell, A. Wilson, A. Z. Pietrzykowski, and S. N. Treistman Acute Alcohol Tolerance Is Intrinsic to the BKCa Protein, but Is Modulated by the Lipid Environment J. Biol. Chem., February 22, 2008; 283(8): 5090 - 5098. [Abstract] [Full Text] [PDF]

				T. Fischer, L. Lu, H. T. Haigler, and R. Langen Annexin B12 Is a Sensor of Membrane Curvature and Undergoes Major Curvature-dependent Structural Changes J. Biol. Chem., March 30, 2007; 282(13): 9996 - 10004. [Abstract] [Full Text] [PDF]

				C. Yuan, R. J. O'Connell, R. F. Jacob, R. P. Mason, and S. N. Treistman Regulation of the Gating of BKCa Channel by Lipid Bilayer Thickness J. Biol. Chem., March 9, 2007; 282(10): 7276 - 7286. [Abstract] [Full Text] [PDF]