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大学・研究所にある論文を検索できる 「Disrupted Cav1.2 Selectivity Causes Overlapping Long QT and Brugada Syndrome Phenotypes in CACNA1C-E1115K iPS Cell Model」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

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Disrupted Cav1.2 Selectivity Causes Overlapping Long QT and Brugada Syndrome Phenotypes in CACNA1C-E1115K iPS Cell Model

Kashiwa, Asami 京都大学 DOI:10.14989/doctor.k24485

2023.03.23

概要

Background
A missense mutation, in the α1c-subunit of voltage-gated L-type Ca2+ channel (LTCC)-coding
CACNA1C-E1115K, located in the Ca2+ selectivity site, causes a variety of arrhythmogenic
phenotypes.
Objective
We aimed to investigate the electrophysiological features and pathophysiological mechanisms of
CACNA1C-E1115K in patient-specific induced pluripotent stem cell (iPSC)-derived cardiomyocytes
(CMs).
Methods
We generated iPSCs from a patient carrying heterozygous CACNA1C-E1115K with overlapping
phenotypes of long QT syndrome, Brugada syndrome, and mild cardiac dysfunction.
Electrophysiological properties were investigated utilizing iPSC-CMs. We used iPSCs from a
healthy subject and an isogenic iPSC line corrected using CRISPR-Cas9-mediated gene editing as
controls. The mathematical E1115K-CM model was developed using a human ventricular cell
model.
Results
Patch-clamp analysis revealed that E1115K-iPSC-CMs exhibited reduced peak Ca2+ current density
and impaired Ca2+ selectivity, with an increased permeability to monovalent cations. ...

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