Unique Cardiac Purkinje Fiber Transient Outward Current β-Subunit Composition

• DOI: 10.1161/circresaha.112.300227
• Publication Date: 2013-03-27T04:54:43Z
• Authors: Ling Xiao; Tamara T. Koopmann; Balázs Ördög; Pieter G. Postema; Arie O. Verkerk; Vivek Iyer; Kevin J. Sampson; Gerard J.J. Boink; Maya A. Mamarbachi; Andras Varro; Luc Jordaens; Jan Res; Robert S. Kass; Arthur A. Wilde; C.R. Bezzina; Stanley Nattel
• Keywords: Purkinje fibers; Transient (computer programming)

A chromosomal haplotype producing cardiac overexpression of dipeptidyl peptidase-like protein-6 (DPP6) causes familial idiopathic ventricular fibrillation. The molecular basis transient outward current (I(to)) in Purkinje fibers (PFs) is poorly understood. We hypothesized that DPP6 contributes to PF I(to) and its might specifically alter properties repolarization.To assess the potential role I(to).Clinical data 5 fibrillation patients suggested arrhythmia origin PF-conducting system. muscle had similar density, but differed from having tetraethylammonium sensitivity slower recovery. significantly increased, whereas knockdown reduced, density canine not cells. K(+)-channel interacting β-subunit protein type-2, essential for normal expression muscle, was weakly expressed human PFs, frequenin (neuronal calcium sensor-1) were enriched. Heterologous Kv4.3 Chinese hamster ovary cells produced small I(to); amplitude greatly enhanced by coexpression with type-2 or DPP6. Coexpression failed compared Kv4.3/K(+)-channel alone, neuronal sensor-1 (to mimic composition) Kv4.3/neuronal recapitulated characteristic kinetic/pharmacological properties. mathematical model action potentials showed enhancement can accelerate repolarization.These results point a previously unknown central I(to), gain function selectively enhancing current, suggest DPP6-mediated early-repolarization syndrome be novel paradigm some forms