STIM1-Ca2+ signaling modulates automaticity of the mouse sinoatrial node

Area of Science:

• Cardiovascular Biology
• Cellular Physiology
• Molecular Cardiology

Background:

• Cardiac pacemaking relies on sinoatrial node cells (SANCs) integrating electrical and calcium signals.
• The interplay between the membrane clock and Ca(2+) clock governs heart rate regulation.

Purpose of the Study:

• To investigate the role of stromal interaction molecule 1 (STIM1) and Orai1 channels in SANCs.
• To elucidate the contribution of STIM1 to cardiac pacemaking and SAN function.

Main Methods:

• Utilized cardiac-specific STIM1 deletion in mice.
• Assessed SAN cell (SANC) function, sarcoplasmic reticulum (SR) Ca(2+) stores, and ionic currents.
• Examined autonomic responses to cholinergic signaling.

Main Results:

• STIM1 and Orai1 channels are selectively expressed in SANCs.
• Cardiac-specific STIM1 deletion led to SR Ca(2+) store depletion and SAN dysfunction.
• STIM1 deletion caused reduced heart rate, sinus arrest, and exaggerated cholinergic response.
• STIM1 regulates store-operated Ca(2+) entry, L-type Ca(2+) current, and Na(+)/Ca(2+) exchanger activity in SANCs.

Conclusions:

• STIM1 is a key regulator of Ca(2+) dynamics in SANCs.
• STIM1 links SR Ca(2+) store content to plasma membrane electrical events.
• STIM1 plays a critical role in maintaining SAN automaticity and cardiac rhythm.