Phenotype-dependent role of the L-type calcium current in embryonic stem cell derived cardiomyocytes

American Journal of Stem Cells

Ying Li¹  Leif Hove-Madsen¹  Zheng Zeng¹  Pauline Dan¹  Yang Qu¹  Glen F Tibbits¹ 

关键词: Pacemaker cells;    cardiac electrophysiology;    cardiomyocyte;    automaticity;   

DOI  :  

学科分类：分子生物学，细胞生物学和基因

来源: e-Century Publishing Corporation

【 摘 要 】

Although the L-type Ca²⁺ current (I_Ca,L) plays an important role in cardiac contractility and pacemaking, its role in embryonic stem-cell derived cardiomyocytes (ESC-CMs) has not yet been explored in detail. We used patch-clamp techniques to characterize I_Ca,L, action potential properties, and nifedipine (an I_Ca,L blocker) sensitivity on spontaneously contracting embryoid bodies (EBs) or isolated ESC-CMs. Cellular preparations exhibited differential sensitivity to nifedipine, with substantial variation in the dose required to abolish automaticity. Isolated ESC-CMs expressing nodal-like action potentials were highly sensitive to nifedipine; 1 nM significantly decreased firing rate, diastolic depolarization rate (DDR), and upstroke velocity, and 10 nM completely abolished spontaneous activity. In contrast, ESC-CMs expressing atrial-like action potentials were relatively nifedipine-resistant, requiring 10 μM to arrest automaticity; 1 μM significantly decreased upstroke velocity while the firing rate and DDR were unaffected. Nodal-like cells exhibited a more negative voltage for half-maximal I_Ca activation (-30 ± 1 mV vs. -20 ± 3 mV; p<0.05) and slower inactivation (71 ± 10 ms vs. 43 ± 3 ms; p<0.05) than atrial-like cells. Our data indicate that I_Ca,L differentially regulates automaticity and chronotropy in nodal-like ESC-CMs, and primarily links excitation to contraction in atrial-like ESC-CMs by contributing to the upstroke phase of the action potential.

【 授权许可】

Unknown