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The Mutation P.T613a in the Pore Helix of the K v 11.1 Potassium Channel is Associated with Long QT Syndrome
Author(s) -
POULSEN KRISTIAN L.,
HOTAIT MOSTAFA,
CALLOE KIRSTINE,
KLAERKE DAN A.,
REBEIZ ABDALLAH,
NEMER GEORGES,
TEJADA MARIA A.,
REFAAT MARWAN M.
Publication year - 2015
Publication title -
pacing and clinical electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.686
H-Index - 101
eISSN - 1540-8159
pISSN - 0147-8389
DOI - 10.1111/pace.12693
Subject(s) - medicine , long qt syndrome , mutation , potassium , potassium channel , helix (gastropod) , short qt syndrome , cardiology , genetics , qt interval , gene , metallurgy , biology , ecology , materials science , snail
Background Loss‐of‐function mutations in the voltage gated potassium channel K v 11.1 have been associated with the Long QT Syndrome (LQTS) type 2. We identified the p.T613A mutation in K v 11.1 in a family with LQTS. T613A is located in the outer part of the pore helix, a structure that is involved in C‐type inactivation. Here we characterize the effect of p.T613A on the functional properties of K V 11.1. Methods The p.T613A mutation was introduced into K V 11.1 (T613A). Wild‐type K V 11.1 (WT) and T613A were expressed in Xenopus laevis oocytes and characterized by two‐electrode‐voltage‐clamp. Results T613A currents were reduced to <20% of WT currents and T613A induced a minor negative shift in half maximal rectification, indicating that the voltage‐dependent onset on inactivation occurred at more negative voltages compared to WT. Co‐expression of T613A with WT revealed intermediate phenotype and there was no dominant negative effect of T613A. Conclusion These findings suggest that p.T613A causes a loss‐of‐function of K v 11.1. This results in a reduced repolarizing reserve which may result in LQTS2 and sudden cardiac death.