The Mutation P.T613a in the Pore Helix of the Kv 11.1 Potassium Channel is Associated with Long QT Syndrome.

Abstract

BACKGROUND:

Loss-of-function mutations in the voltage gated potassium channel Kv 11.1 have been associated with the Long QT Syndrome (LQTS) type 2. We identified the p.T613A mutation in Kv 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 KV 11.1.

METHODS:

The p.T613A mutation was introduced into KV 11.1 (T613A). Wild-type KV 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 Kv 11.1. This results in a reduced repolarizing reserve which may result in LQTS2 and sudden cardiac death.

• Authors: Kristian L Poulsen, Mostafa Hotait, Kirstine Calloe, Dan A Klaerke, Abdallah Rebeiz, Georges Nemer, Maria A Tejada, Marwan M Refaat
• Journal: Pacing and clinical electrophysiology : PACE (Pacing Clin Electrophysiol) Vol. 38 Issue 11 Pg. 1304-9 (Nov 2015) ISSN: 1540-8159 [Electronic] United States
• PMID: 26173150 (Publication Type: Case Reports, Journal Article)
• Copyright: © 2015 Wiley Periodicals, Inc.

Chemical References

• ERG1 Potassium Channel
• KCNH2 protein, human
• Potassium Channels

Topics

• Death, Sudden, Cardiac (etiology)
• ERG1 Potassium Channel (genetics)
• Fatal Outcome
• Humans
• Long QT Syndrome (complications, genetics)
• Male
• Mutation
• Pedigree
• Potassium Channels (genetics)
• Young Adult