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. 2015 Jun 19;6:118. doi: 10.3389/fphar.2015.00118

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Copyright © 2015 O’Leary and Chahine.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Methanethiosulfonate reagent inhibition requires fast inactivation. The V1763C and Y1767C mutations were transferred to an inactivation deficient background of Na_v1.5 created by replacing the conserved F1486 of the interdomain D3–D4 linker with either cysteine or glutamine (see text). (A) Shows the current of the ICM mutant lacking D4S6 mutations measured during perfusion with standard pipette solution. (B) Current of the V1767C-ICM mutant measured with 1 mM MTSET in the patch pipette. (C) Current of the Y1767C-ICM mutant measured in the presence of MTSET. (D) Currents were measured immediately after break in (P₁) and after 5 min (P₆₀). The P₆₀/P₁ ratios of the V1763C-ICM and Y1767C-ICM mutants were not different after 5 min of internal MTSET. Also shown are the P₆₀/P₁ ratios of the non-inactivating V1763C-IQM and Y1767C-IQM mutants.