Emerging Concepts in Ion Channel Biophysics

Emerging Concepts in Ion Channel Biophysics

Poster Abstracts

60-POS Board 60 Molecular Determinants of Ion Permeation and Selectivity in Voltage-gated Bacterial Sodium Channel Na v Ab Christopher Ing 1,2 , Nilmadhab Chakrabarti 1 , Ning Zheng 3,4 , William A. Catterall 3 , Régis Pomès 1,2 . 1 Hospital for Sick Children, Toronto, ON, Canada, 2 University of Toronto, Toronto, ON, Canada, 3 University of Washington, Seattle, WA, USA, 4 Howard Hughes Medical Institute, Seattle, WA, USA. The determination of high-resolution structures of voltage-gated Na + channels has opened the way to elucidating the mechanism of sodium permeation and selectivity. Molecular simulation studies of bacterial sodium channel Na v Ab suggest that Na + binding and permeation through the selectivity filter are coupled to the conformational isomerization of the Glu177 side chains of the EEEE ring from an outfacing conformation to a lumen-facing conformation, resulting in a high rate of Na + diffusion through the selectivity filter. To clarify the role of channel dynamics on ion permeation and selectivity, we examine the mechanism of Na + and K + permeation in various systems in which either the nature of the EEEE ring or the extent of channel fluctuations have been modified. Extensive molecular dynamics simulations performed in the presence of NaCl, KCl, or a mixture of the two, show how modifying the structure and fluctuations of the selectivity filter alters the conduction mechanism and the competitive binding of Na + and K + . These findings suggest that conformational fluctuations of the EEEE ring play an important role in the ionic selectivity of voltage-gated Na + channels.

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