An LQTS6 MiRP1 mutation suppresses pacemaker current and is associated with sinus bradycardia.

ABSTRACT:

Background

Sinus node (SN) dysfunction is observed in some long-QT syndrome (LQTS) patients, but has not been studied as a function of LQTS genotype. LQTS6 involves mutations in the hERG β-subunit MiRP1, which also interacts with hyperpolarization-activated, cyclic nucleotide gated (HCN) channels-the molecular correlate of SN pacemaker current (If ). An LQTS registry search identified a 55-year male with M54T MiRP1 mutation, history of sinus bradycardia (39-56 bpm), and prolonged QTc.

Objective

We tested if LQTS6 incorporates sinus bradycardia due to abnormal If .

Methods

We transiently co-transfected neonatal rat ventricular myocytes (to study currents in a myocyte background) with human HCN4 (hHCN4, primary SN isoform) or human HCN2 (hHCN2) and one of the following:

SUBMITTER: Nawathe PA 

PROVIDER: S-EPMC4059362 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature