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Updated: Jul 8, 2026
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Single-Cell Optical Action Potential Measurement in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Published on: December 22, 2020
G(o) controls the hyperpolarization-activated current in embryonic stem cell-derived cardiocytes
Chian P Ye1, Sheng Zhong Duan, David S Milstone
1Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
American Journal of Physiology. Heart and Circulatory Physiology
|December 25, 2007
Summary
Heart rate regulation involves the hyperpolarization-activated current (I(f)). This study shows G(o) protein is essential for muscarinic inhibition of I(f) under basal conditions, but not after beta-agonist stimulation.
Area of Science:
- Cardiology
- Molecular Biology
- Electrophysiology
Background:
- The hyperpolarization-activated current (I(f)) is crucial for controlling heart rate.
- I(f) activity is modulated by cyclic AMP (cAMP) and inhibited by pertussis toxin-sensitive G-proteins G(i)/G(o).
Purpose of the Study:
- To investigate the specific roles of G(o) and G(i) proteins in regulating I(f) activity in cardiocytes derived from embryonic stem cells.
- To elucidate the mechanisms underlying muscarinic inhibition of I(f), including the involvement of nitric oxide.
Main Methods:
- Derivation of cardiocytes from embryonic stem cells genetically modified to lack specific G-proteins (G(o), G(i2), G(i3)).
- Electrophysiological recordings to measure basal and stimulated I(f) activity.
- Assessment of muscarinic inhibition and beta-adrenergic stimulation effects on I(f).
Main Results:
- Cardiocytes lacking G(o), G(i2), or G(i3) exhibited normal basal and isoproterenol-stimulated I(f) activity.
- Under basal conditions, both G(o) and G(i) were required for muscarinic inhibition of I(f), involving nitric oxide production.
- After beta-agonist stimulation, only G(o) was necessary for muscarinic inhibition, independent of G(i) and nitric oxide.
Conclusions:
- G(o) protein plays a critical role in the antiadrenergic effect of muscarinic agents on I(f).
- The regulatory pathways for I(f) differ between basal and beta-adrenergically stimulated states.
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