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Please use this identifier to cite or link to this item: http://dspace.utalca.cl/handle/1950/9171

Title: K+ Conduction and Mg2+ Blockade in a Shaker Kv-Channel Single Point Mutant with an Unusually High Conductance
Authors: Moscoso, C.
Vergara-Jaque, A.
Márquez-Miranda, V.
Sepúlveda, R.V.
Valencia, I.
Díaz-Franulic, I.
González-Nilo, F.
Naranjo, D.
Issue Date: 19-Sep-2012
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
URI: http://dspace.utalca.cl/handle/1950/9171
ISSN: 0006-3495
Appears in Collections:Artículos en publicaciones ISI - Universidad de Talca

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