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Increases of T-type Ca2+ current in heart cells of the cardiomyopathic hamster
G Bkaily1, A Sculptoreanu, D Jacques
1Department of Anatomy and Cell Biology, Faculty of Medicine, Université de Sherbrooke, Quebec, Canada.
Insights
Hereditary cardiomyopathy in hamsters shows altered T-type calcium channel (ICa(T)) activity, with increased current density and window current in affected heart cells, potentially explaining calcium overload. L-type calcium channel (ICa(L)) properties remained similar between normal and diseased hamsters.
Area of Science:
- Cardiovascular Physiology
- Cellular Electrophysiology
- Cardiac Pathophysiology
Background:
- Hereditary cardiomyopathies can lead to significant alterations in cardiac function.
- Calcium ion (Ca2+) handling is crucial for cardiomyocyte excitation-contraction coupling and is often dysregulated in heart disease.
Purpose of the Study:
- To investigate and compare T-type and L-type calcium channel currents (ICa(T) and ICa(L)) in heart cells from normal and hereditary cardiomyopathic hamsters.
- To identify electrophysiological differences that may contribute to the pathophysiology of cardiomyopathy.
Main Methods:
- Utilized the whole-cell voltage clamp technique to record ionic currents in isolated single heart cells.
- Examined both normal and cardiomyopathic hamster models at newborn and young stages.
Main Results:
- L-type calcium channel (ICa(L)) current-voltage relationships and kinetics were similar in both normal and cardiomyopathic cells, but a higher proportion of cardiomyopathic cells exhibited ICa(L).
- T-type calcium channel (ICa(T)) current-voltage relationships were also similar, yet cardiomyopathic cells showed a larger window current and a greater proportion of ventricular myocytes displayed ICa(T).
- Higher density, larger window current, and increased prevalence of ICa(T) in cardiomyopathic hearts may contribute to observed Ca2+ overload.
Conclusions:
- Altered T-type calcium channel (ICa(T)) activity, characterized by increased density and window current, is a significant finding in hereditary cardiomyopathic hamster hearts.
- These ICa(T) alterations may play a role in the calcium overload characteristic of this cardiac disease model.
- While L-type calcium channel (ICa(L)) expression differs, its functional properties are not significantly altered in this model.
Abstract:
In the present study, the whole-cell voltage clamp technique was used in order to record the T- and L-type Ca2+ currents in single heart cells of newborn and young normal and hereditary cardiomyopathic hamsters. Our results showed that the I/V relationship curve as well as the kinetics of the L-type Ca2+ currents (ICa(L)) in both normal and cardiomyopathic heart cells were the same. However, the proportion of myocytes from normal heart hamster that showed L-type ICa was less than that of heart cells from cardiomyopathic hamster. The I/V relationship curve of the T-type ICa (ICa(T)) was the same in myocytes of both normal and cardiomyopathic hamsters. The main differences between ICa(T) of cardiomyopathic and normal hamster are a larger window current and the proportion of ventricular myocytes that showed this type of current in cardiomyopathic hamster. The high density of ICa(T) as well as the large window current and proportion of myocytes showing ICa(T) may explain in part Ca2+ overload observed in cardiomyopathic heart cells of the hamster.