Calcium signaling consequences of RyR2 mutations associated with CPVT1 introduced via CRISPR/Cas9 gene editing in human-induced pluripotent stem cell-derived cardiomyocytes: Comparison of RyR2-R420Q, F2483I, and Q4201R.

ABSTRACT:

Background

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) created from patients with catecholaminergic polymorphic ventricular tachycardia 1 (CPVT1) have been used to study CPVT1 arrhythmia.

Objective

The purpose of this study was to evaluate the Ca²⁺ signaling aberrancies and pharmacological sensitivities of 3 CRISPR/Cas9-introduced CPVT1 mutations located in different molecular domains of ryanodine receptor 2 (RyR2).

Methods

CRISPR/Cas9-engineered hiPSC-CMs carrying RyR2 mutations-R420Q, Q4201R, and F2483I-were voltage clamped, and their electrophysiology, pharmacology, and Ca²⁺ signaling phenotypes measured using total internal reflection fluorescence microscopy.

Results

R420Q and Q4201R mutant hiPSC-CMs exhibit

SUBMITTER: Zhang XH 

PROVIDER: S-EPMC7893824 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature