scholarly journals The Selectivity Filter of the Voltage-gated Sodium Channel Is Involved in Channel Activation

2001 ◽  
Vol 276 (30) ◽  
pp. 27831-27839 ◽  
Author(s):  
Karlheinz Hilber ◽  
Walter Sandtner ◽  
Oliver Kudlacek ◽  
Ian W. Glaaser ◽  
Eva Weisz ◽  
...  
2016 ◽  
Vol 113 (48) ◽  
pp. 13762-13767 ◽  
Author(s):  
Monica N. Kinde ◽  
Vasyl Bondarenko ◽  
Daniele Granata ◽  
Weiming Bu ◽  
Kimberly C. Grasty ◽  
...  

Voltage-gated sodium channels (NaV) play an important role in general anesthesia. Electrophysiology measurements suggest that volatile anesthetics such as isoflurane inhibit NaVby stabilizing the inactivated state or altering the inactivation kinetics. Recent computational studies suggested the existence of multiple isoflurane binding sites in NaV, but experimental binding data are lacking. Here we use site-directed placement of19F probes in NMR experiments to quantify isoflurane binding to the bacterial voltage-gated sodium channel NaChBac.19F probes were introduced individually to S129 and L150 near the S4–S5 linker, L179 and S208 at the extracellular surface, T189 in the ion selectivity filter, and all phenylalanine residues. Quantitative analyses of19F NMR saturation transfer difference (STD) spectroscopy showed a strong interaction of isoflurane with S129, T189, and S208; relatively weakly with L150; and almost undetectable with L179 and phenylalanine residues. An orientation preference was observed for isoflurane bound to T189 and S208, but not to S129 and L150. We conclude that isoflurane inhibits NaChBac by two distinct mechanisms: (i) as a channel blocker at the base of the selectivity filter, and (ii) as a modulator to restrict the pivot motion at the S4–S5 linker and at a critical hinge that controls the gating and inactivation motion of S6.


2015 ◽  
Vol 108 (2) ◽  
pp. 490a
Author(s):  
Claire E. Naylor ◽  
Claire Bagneris ◽  
Paul G. DeCaen ◽  
David E. Clapham ◽  
B.A. Wallace

Neuron ◽  
2016 ◽  
Vol 89 (6) ◽  
pp. 1355
Author(s):  
Wolfgang G. Bywalez ◽  
Dinu Patirniche ◽  
Vanessa Rupprecht ◽  
Martin Stemmler ◽  
Andreas V.M. Herz ◽  
...  

Circulation ◽  
2002 ◽  
Vol 106 (16) ◽  
pp. 2098-2103 ◽  
Author(s):  
Caroline Pinet ◽  
Bruno Le Grand ◽  
Gareth W. John ◽  
Alain Coulombe

Neuron ◽  
2015 ◽  
Vol 85 (3) ◽  
pp. 590-601 ◽  
Author(s):  
Wolfgang G. Bywalez ◽  
Dinu Patirniche ◽  
Vanessa Rupprecht ◽  
Martin Stemmler ◽  
Andreas V.M. Herz ◽  
...  

Cell Research ◽  
2012 ◽  
Vol 23 (3) ◽  
pp. 409-422 ◽  
Author(s):  
Xu Zhang ◽  
Mengdie Xia ◽  
Yang Li ◽  
Huihui Liu ◽  
Xin Jiang ◽  
...  

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