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|Title: ||K+ Conduction and Mg2+ Blockade in a Shaker Kv-Channel Single Point Mutant with an Unusually High Conductance|
|Authors: ||Moscoso, C.|
|Issue Date: ||19-Sep-2012 |
|Publisher: ||CELL PRESS, 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA|
|Citation: ||BIOPHYSICAL JOURNAL Volume: 103 Issue: 6 Pages: 1198-1207|
|Abstract: ||Potassium channels exhibit a large diversity of single-channel conductances. Shaker is a low-conductance K-channel in which Pro475 -> Asp, a single-point mutation near the internal pore entrance, promotes 6- to 8-fold higher unitary current. To assess the mechanism for this higher conductance, we measured Shaker-P475D single-channel current in a wide range of symmetrical K+ concentrations and voltages. Below 300 mM K+, the current-to-voltage relations (i-V) showed inward rectification that disappeared at 1000 mM K+. Single-channel conductance reached a maximum of similar to 190 pS at saturating [K+], a value 4- to 5-fold larger than that estimated for the native channel. Intracellular Mg2+ blocked this variant with similar to 100-fold higher affinity. Near zero voltage, blockade was competitively antagonized by K+; however, at voltages >100 mV, it was enhanced by K+. This result is consistent with a lock-in effect in a single-file diffusion regime of Mg2+ and K+ along the pore. Molecular-dynamics simulations revealed higher K+ density in the pore, especially near the Asp-475 side chains, as in the high-conductance MthK bacterial channel. The molecular dynamics also showed that K+ ions bound distally can coexist with other K+ or Mg2+ in the cavity, supporting a lock-in mechanism. The maximal K+ transport rate and higher occupancy could be due to a decrease in the electrostatic energy profile for K+ throughout the pore, reducing the energy wells and barriers differentially by similar to 0.7 and similar to 2 kT, respectively.|
|Description: ||Vergara-Jaque, A (Vergara-Jaque, Ariela). Univ Talca, Ctr Bioinformat & Simulac Mol, Talca, Chile|
|Appears in Collections:||Artículos en publicaciones ISI - Universidad de Talca|
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