The calcium and voltage clocks in sinoatrial node automaticity.

Area of Science:

• Cardiology
• Electrophysiology
• Molecular Biology

Background:

• The sinoatrial node (SAN) controls heart rate through coordinated electrical activity.
• Voltage and Ca2+ clocks are known regulators of SAN automaticity.
• The SAN is heterogeneous, suggesting regional variations in clock importance.

Purpose of the Study:

• To investigate the synergistic roles of voltage and Ca2+ clocks in SAN automaticity.
• To determine how beta-adrenergic stimulation affects SAN pacemaker activity and clock function.
• To map intracellular calcium and membrane potentials in the intact SAN.

Main Methods:

• Simultaneous optical mapping of intracellular calcium (Cai) and membrane potentials in isolated, Langendorff-perfused canine right atria.
• Utilized criteria for late diastolic Cai elevation (LDCAE) timing relative to action potential upstroke to detect Ca2+ clock activity.
• Analyzed changes in sinus rate and pacemaker shift during beta-adrenergic stimulation.

Main Results:

• Beta-adrenergic stimulation increased sinus rate and shifted the leading pacemaker to the superior SAN.
• A robust LDCAE, indicative of Ca2+ clock activity, was observed during stimulation.
• LDCAE was attributed to spontaneous diastolic SR Ca2+ release and correlated with heart rate changes.

Conclusions:

• The Ca2+ clock, driven by spontaneous sarcoplasmic reticulum Ca2+ release, plays a crucial role in regulating SAN automaticity.
• Voltage and Ca2+ clocks operate synergistically to generate SAN automaticity.
• Pacemaker function is regionally variable within the SAN, influenced by Ca2+ clock activity.