Reciprocal voltage sensor-to-pore coupling leads to potassium channel C-type inactivation.
Voltage-gated potassium channels open at depolarized membrane voltages. A prolonged depolarization causes a rearrangement of the selectivity filter which terminates the conduction of ions - a process called slow or C-type inactivation. How structural rearrangements in the voltage-sensor domain (VSD) cause alteration in the selectivity filter, and vice versa, are not fully understood. We show that pulling the pore domain of the Shaker potassium channel towards the VSD by a Cd(2+) bridge accelerates C-type inactivation. Molecular dynamics simulations show that such pulling widens the selectivity filter and disrupts the K(+) coordination, a hallmark for C-type inactivation. An engineered Cd(2+) bridge within the VSD also affect C-type inactivation. Conversely, a pore domain mutation affects VSD gating-charge movement. Finally, C-type inactivation is caused by the concerted action of distant amino acid residues in the pore domain. All together, these data suggest a reciprocal communication between the pore domain and the VSD in the extracellular portion of the channel.
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Luca
L
Conti
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Jakob
J
Renhorn
Theoretical and Computational Biophysics, Department of Theoretical Physics, KTH Royal Institute of Technology, Stockholm, Sweden.
Anders
A
Gabrielsson
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Fredrik
F
Turesson
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Sara I
SI
Liin
Theoretical and Computational Biophysics, Department of Theoretical Physics, KTH Royal Institute of Technology, Stockholm, Sweden.|Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Erik
E
Lindahl
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Fredrik
F
Elinder
D000818:Animals; D002104:Cadmium / Q000737:chemistry; D017353:Gene Deletion; D015640:Ion Channel Gating; D008564:Membrane Potentials / Q000502:physiology; D056004:Molecular Dynamics Simulation; D009154:Mutation; D011188:Potassium / Q000737:chemistry; D000072417:Protein Domains; D051637:Shaker Superfamily of Potassium Channels / Q000737:chemistry*; D055672:Static Electricity; D014982:Xenopus laevis
D051637:Shaker Superfamily of Potassium Channels; D002104:Cadmium; D011188:Potassium