Initial steps of inactivation at the K+ channel selectivity filter.

نویسندگان

  • Andrew S Thomson
  • Florian T Heer
  • Frank J Smith
  • Eunan Hendron
  • Simon Bernèche
  • Brad S Rothberg
چکیده

K(+) efflux through K(+) channels can be controlled by C-type inactivation, which is thought to arise from a conformational change near the channel's selectivity filter. Inactivation is modulated by ion binding near the selectivity filter; however, the molecular forces that initiate inactivation remain unclear. We probe these driving forces by electrophysiology and molecular simulation of MthK, a prototypical K(+) channel. Either Mg(2+) or Ca(2+) can reduce K(+) efflux through MthK channels. However, Ca(2+), but not Mg(2+), can enhance entry to the inactivated state. Molecular simulations illustrate that, in the MthK pore, Ca(2+) ions can partially dehydrate, enabling selective accessibility of Ca(2+) to a site at the entry to the selectivity filter. Ca(2+) binding at the site interacts with K(+) ions in the selectivity filter, facilitating a conformational change within the filter and subsequent inactivation. These results support an ionic mechanism that precedes changes in channel conformation to initiate inactivation.

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عنوان ژورنال:
  • Proceedings of the National Academy of Sciences of the United States of America

دوره 111 17  شماره 

صفحات  -

تاریخ انتشار 2014