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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Putative resolution of the EEEE selectivity paradox in L-type Ca2+ and bacterial Na+ biological ion channels
AU - Kaufman, Igor Kh
AU - Luchinsky, Dmitrii Georgievich
AU - Gibby, William A. T.
AU - McClintock, Peter Vaughan Elsmere
AU - Eisenberg, R. S.
PY - 2016/5/20
Y1 - 2016/5/20
N2 - The highly selective permeation of ions through biological ion channels can be described and explained in terms of fluctuational dynamics under the influence of powerful electrostatic forces. Hence valence selectivity, e.g. between Ca2+ and Na+ in calcium and sodium channels, can be described in terms of ionic Coulomb blockade, which gives rise to distinct conduction bands and stop-bands as the fixed negative charge Qf at the selectivity filter of the channel is varied. This picture accounts successfully for a wide range of conduction phenomena in a diversity of ion channels. A disturbing anomaly, however, is that what appears to be the same electrostatic charge and structure (the so-called EEEE motif) seems to select Na+ conduction in bacterial channels but Ca2+ conduction in mammalian channels. As a possible resolution of this paradox it is hypothesised that an additional charged protein residue on the permeation path of the mammalian channel increases |Qf | by e, thereby altering the selectivity from Na+ to Ca2+. Experiments are proposed that will enable the hypothesis to be tested.
AB - The highly selective permeation of ions through biological ion channels can be described and explained in terms of fluctuational dynamics under the influence of powerful electrostatic forces. Hence valence selectivity, e.g. between Ca2+ and Na+ in calcium and sodium channels, can be described in terms of ionic Coulomb blockade, which gives rise to distinct conduction bands and stop-bands as the fixed negative charge Qf at the selectivity filter of the channel is varied. This picture accounts successfully for a wide range of conduction phenomena in a diversity of ion channels. A disturbing anomaly, however, is that what appears to be the same electrostatic charge and structure (the so-called EEEE motif) seems to select Na+ conduction in bacterial channels but Ca2+ conduction in mammalian channels. As a possible resolution of this paradox it is hypothesised that an additional charged protein residue on the permeation path of the mammalian channel increases |Qf | by e, thereby altering the selectivity from Na+ to Ca2+. Experiments are proposed that will enable the hypothesis to be tested.
KW - Biological ion channels
KW - Coulomb blockade
KW - Stochastic dynamics
KW - EEEE paradox
KW - Brownian motion
KW - stochastic processes (theory)
KW - dynamics (theory)
KW - diffusion
U2 - 10.1088/1742-5468/2016/05/054027
DO - 10.1088/1742-5468/2016/05/054027
M3 - Journal article
VL - 2016
JO - Journal of Statistical Mechanics: Theory and Experiment
JF - Journal of Statistical Mechanics: Theory and Experiment
SN - 1742-5468
M1 - 054027
ER -