Stretch-Induced Increase in Ca²⁺-Spark Rate in Rabbit Atrial Cardiomyocytes Requires TRPA1 and Intact...

Area of Science:

• Cardiovascular Physiology
• Cellular Electrophysiology
• Mechanotransduction

Background:

• Mechanical stretch in the heart can trigger arrhythmias by altering cellular calcium (Ca2+) handling.
• Cation nonselective mechano-sensitive ion channels are potential mediators of these stretch-induced effects.

Purpose of the Study:

• To investigate the presence of stretch-induced increases in Ca2+-spark rate (SiS) in isolated atrial cardiomyocytes.
• To elucidate the underlying mechanisms of this phenomenon.

Main Methods:

• Isolated atrial cardiomyocytes from rabbits, pigs, and humans were subjected to axial mechanical stretch.
• Cytosolic Ca2+ was monitored using confocal microscopy under resting and stretched conditions.

Main Results:

• Diastolic stretch significantly increased SiS.
• This increase was dependent on microtubule integrity and transsarcolemmal Na+ or Ca2+ influx.
• TRPA1 channel activation increased baseline spark rate, which was further enhanced by stretch, while Piezo1 activation showed a similar but less pronounced effect.
• SiS was blocked by TRPA1 inhibitors, indicating TRPA1's critical role.

Conclusions:

• Diastolic stretch enhances Ca2+-spark rate in atrial cardiomyocytes through a mechanism involving microtubule integrity and TRPA1 channels.
• Redox signaling is not involved in this process.
• TRPA1 is identified as a key regulator of stretch-induced Ca2+ handling in atrial cells, with significant implications for cardiac arrhythmogenesis.