Excitation-contraction coupling in the day 15 embryonic chick heart with persistent truncus arteriosus

Area of Science:

• Cardiovascular Research
• Developmental Biology
• Molecular Cardiology

Background:

• Neural crest-related heart defects, such as persistent truncus arteriosus (PTA), are associated with high prenatal mortality.
• Previous studies suggest reduced L-type Ca2+ current in PTA hearts, hinting at impaired cardiac excitation-contraction coupling.
• Altered myocardial development is suspected in these defects, beyond structural anomalies.

Purpose of the Study:

• To investigate the role of calcium (Ca2+) transients in the pathophysiology of persistent truncus arteriosus (PTA).
• To determine if impaired cardiac excitation-contraction coupling contributes to the poor viability observed in PTA embryos.

Main Methods:

• Direct measurement of systolic Ca2+ transients in fura-2-loaded cardiomyocytes from normal and PTA embryonic chick hearts.
• Assessment of L-type Ca2+ current and response to isoproterenol (ISO).
• Evaluation of caffeine-stimulated Ca2+ transients and sarcoplasmic reticulum (SR) function.

Main Results:

• Ca2+ transients were significantly depressed in hearts with PTA, often requiring signal averaging or ISO treatment for detection.
• Reduced L-type Ca2+ current was confirmed as a partial cause of depressed Ca2+ transients.
• ISO normalized L-type Ca2+ current but did not fully restore Ca2+ transients; caffeine-stimulated transients were diminished and slowed, indicating impaired SR function.

Conclusions:

• Persistent truncus arteriosus (PTA) is associated with severely impaired cardiac excitation-contraction coupling.
• Both reduced L-type Ca2+ current and sarcoplasmic reticulum (SR) dysfunction contribute to the depressed Ca2+ transients in PTA hearts.
• Impaired cardiac excitation-contraction coupling is a likely cause of poor embryonic viability in PTA.