Premium
Developing and testing a quantitative model of ion permeation based on the MacKinnon mechanism
Author(s) -
Sanchez Sabrina Isabel,
Wadowski Alexis,
Nelson Peter Hugo
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1042.24
Subject(s) - ion , permeation , mechanism (biology) , flux (metallurgy) , chemistry , ion channel , lipid bilayer , chemical physics , membrane , materials science , analytical chemistry (journal) , atomic physics , physics , chromatography , biochemistry , quantum mechanics , receptor , organic chemistry
Ion channels are a crucial component of cell membranes that allow ions to pass through the lipid bilayer. Based on the x‐ray structure he discovered, MacKinnon proposed a two‐step permeation mechanism in which the selectivity filter normally contains two ions, either in a 1,3 or a 2,4 configuration. Using this two‐step mechanism, we developed a mathematical model for the flux through the channel. The knock‐off step begins with the ion channel in the 1,3 configuration. An ion then enters site 4 causing a concerted shift of all three ions resulting in a transition from the 1,3 to the 2,4 configuration that simultaneously knocks off the ion initially in site 1. In the translocation step, the channel returns to the 1,3 configuration by a concerted translocation. Based on this mechanism, we developed a three‐parameter mathematical model that includes an electrical distance representing translocation between configurations 2,4 and 1,3. While the model can be successfully fitted to (previously published) experimental single‐channel data, the resulting electrical distance for the translocation step is essentially one. The physical interpretation of this fitted value is problematic as the value of the fitted parameter effectively removes the knock‐off step from the permeation mechanism. Support from the National Science Foundation (NSF Grant DUE‐0836833) is gratefully acknowledged