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Emerging Concepts in Ion Channel Biophysics
Poster Abstracts
110
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.