当前位置： SCI文献检索 > JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY期刊下所有文献 > Identification and characterization of a transient outward K+ current in human induced pluripotent stem cell-derived cardiomyocytes.

Identification and characterization of a transient outward K+ current in human induced pluripotent stem cell-derived cardiomyocytes.

Abstract：

BACKGROUND:The ability to recapitulate mature adult phenotypes is critical to the development of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) as models of disease. The present study examines the characteristics of the transient outward current (Ito) and its contribution to the hiPSC-CM action potential (AP). METHOD:Embryoid bodies were made from a hiPS cell line reprogrammed with Oct4, Nanog, Lin28 and Sox2. Sharp microelectrodes were used to record APs from beating-clusters (BC) and patch-clamp techniques were used to record Ito in single hiPSC-CM. mRNA levels of Kv1.4, KChIP2 and Kv4.3 were quantified from BCs. RESULTS:BCs exhibited spontaneous beating (60.5±2.6 bpm) and maximum-diastolic-potential (MDP) of 67.8±0.8 mV (n=155). A small 4-aminopyridine-sensitive phase-1-repolarization was observed in only 6/155 BCs. A robust Ito was recorded in the majority of cells (13.7±1.9 pA/pF at +40 mV; n=14). Recovery of Ito from inactivation (at -80 mV) showed slow kinetics (τ1=200±110 ms (12%) and τ2=2380±240 ms (80%)) accounting for its minimal contribution to the AP. Transcript data revealed relatively high expression of Kv1.4 and low expression of KChIP2 compared to human native ventricular tissues. Mathematical modeling predicted that restoration of IK1 to normal levels would result in a more negative MDP and a prominent phase-1-repolarization. CONCLUSION:The slow recovery kinetics of Ito coupled with a depolarized MDP account for the lack of an AP notch in the majority of hiPSC-CM. These characteristics reveal a deficiency for the development of in vitro models of inherited cardiac arrhythmia syndromes in which Ito-induced AP notch is central to the disease phenotype.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Cordeiro JM,Nesterenko VV,Sicouri S,Goodrow RJ Jr,Treat JA,Desai M,Wu Y,Doss MX,Antzelevitch C,Di Diego JM

doi

10.1016/j.yjmcc.2013.03.014

subject

Has Abstract

pub_date

2013-07-01 00:00:00

pages

36-46

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(13)00095-3

journal_volume

pub_type

杂志文章

在线工具

Identification and characterization of a transient outward K+ current in human induced pluripotent stem cell-derived cardiomyocytes.