A study on the biophysical properties of NaV1.5 channels in human induced pluripotent stem cell-derived atrial-like and ventricular-like cardiomyocytes
Introduction:
Cardiovascular diseases, including arrhythmias, are a leading cause of morbidity and mortality worldwide. Understanding the biophysical properties of ion channels in cardiac cells is crucial for unraveling the mechanisms underlying these diseases. The NaV1.5 channel plays a vital role in cardiac excitability and conduction, making it an important target for studying arrhythmias. In recent years, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising model for studying cardiac physiology and disease. This article discusses a study that investigated the biophysical properties of NaV1.5 channels in hiPSC-CMs, specifically comparing atrial-like and ventricular-like cardiomyocytes.
Methods:
The study utilized hiPSCs derived from human fibroblasts, which were then differentiated into atrial-like and ventricular-like cardiomyocytes using specific protocols. The researchers performed whole-cell patch-clamp recordings to measure the electrophysiological properties of NaV1.5 channels in these cells. Voltage-clamp protocols were used to assess channel activation, inactivation, recovery from inactivation, and steady-state inactivation. Current-clamp recordings were also conducted to evaluate action potential characteristics.
Results:
The study found distinct differences in the biophysical properties of NaV1.5 channels between atrial-like and ventricular-like hiPSC-CMs. Atrial-like cells exhibited faster activation kinetics compared to ventricular-like cells, with a more positive voltage dependence of activation. Inactivation properties also differed, with atrial-like cells showing slower inactivation kinetics and a more negative voltage dependence of inactivation compared to ventricular-like cells. Recovery from inactivation was faster in atrial-like cells. Additionally, steady-state inactivation curves revealed differences in the voltage range at which NaV1.5 channels were available for activation.
Discussion:
The findings of this study provide valuable insights into the biophysical properties of NaV1.5 channels in hiPSC-CMs, highlighting the heterogeneity between atrial-like and ventricular-like cells. These differences may contribute to the distinct electrophysiological characteristics observed in atrial and ventricular tissues in the human heart. The faster activation kinetics in atrial-like cells suggest a higher propensity for rapid depolarization, potentially contributing to the generation of atrial arrhythmias. The differences in inactivation kinetics and voltage dependence of inactivation may also impact the duration and propagation of action potentials in these cells.
The study’s results align with previous studies conducted on native cardiac tissues, further validating the use of hiPSC-CMs as a model for studying cardiac physiology. However, it is important to note that hiPSC-CMs do not fully recapitulate the complexity of native cardiac tissue, and caution should be exercised when extrapolating these findings to human physiology.
Conclusion:
The study on the biophysical properties of NaV1.5 channels in hiPSC-CMs provides valuable insights into the heterogeneity between atrial-like and ventricular-like cells. The differences observed in activation, inactivation, recovery from inactivation, and steady-state inactivation properties of NaV1.5 channels contribute to our understanding of the mechanisms underlying arrhythmias and may aid in the development of targeted therapies. Further research is needed to explore the functional consequences of these biophysical differences and their implications for cardiac electrophysiology and disease.
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- Source Link: https://platohealth.ai/biophysical-properties-of-nav1-5-channels-from-atrial-like-and-ventricular-like-cardiomyocytes-derived-from-human-induced-pluripotent-stem-cells-scientific-reports/