RT Journal Article
T1 Functional effects of a missense mutation in HERG associated with type 2 long QT syndrome
A1 Amorós García, Irene
A1 Jiménez Jáimez, Juan
A1 Tercedor, Luis
A1 Barana Muñóz, Adriana
A1 Gómez García, Ricardo
A1 González de la Fuente, Marta
A1 Dolz Gaitón, Pablo
A1 Álvarez, Miguel
A1 Martínez Espín, Esther
A1 Lorente, José
A1 Melgares, Rafael
A1 Tamargo Menéndez, Juan
A1 Delpón Mosquera, María Eva
A1 Caballero Collado, Ricardo
AB Background: Long QT syndrome (LQTS) is characterized by a prolonged QT interval that can lead to severe ventricular arrhythmias (torsades de pointes) and sudden death. Congenital LQTS type 2 (LQT2) is due to loss-of-function mutations in the KCNH2 gene encoding Kv11.1 channels responsible for the rapid component of the delayed rectifier current.Objective: The purpose of this study was to determine the functional properties of the LQT2-associated mutation p.E637G found in a Spanish family.Methods: Wild-type (WT) and p.E637G Kv11.1 channels were transiently transfected in Chinese hamster ovary cells, and currents were recorded using the patch-clamp technique.Results: The p.E637G channels lost inward rectification and K(+) selectivity, generating small but measurable slowly activating, noninactivating currents. These important alterations were corrected neither by cotransfection with WT channels nor by incubation at low temperatures or with pharmacological chaperones. As a consequence of its effects on channel gating, the mutation significantly reduced the outward repolarizing current during the action potential (AP), resulting in a marked lengthening of the duration of a simulated human ventricular AP.Conclusion: We have identified and characterized an LQT2-associated mutation that through removal of C-type inactivation and reduction of K(+) selectivity causes the QT prolongation observed in the patients carrying the mutation. Moreover, the results obtained demonstrate the importance of the glutamic acid at position 637 for the inactivation process and K(+) selectivity of Kv11.1 channels.
PB Elsevier
SN 1547-5271
YR 2011
FD 2011
LK https://hdl.handle.net/20.500.14352/92475
UL https://hdl.handle.net/20.500.14352/92475
LA eng
NO Amorós I, Jiménez-Jáimez J, Tercedor L, Barana A, Gómez R, de la Fuente MG, Dolz-Gaitón P, Alvarez M, Martínez-Espín E, Lorente JA, Melgares R, Tamargo J, Delpón E, Caballero R. Functional effects of a missense mutation in HERG associated with type 2 long QT syndrome. Heart Rhythm. 2011 Mar;8(3):463-70. doi: 10.1016/j.hrthm.2010.11.032
DS Docta Complutense
RD 7 jun 2025