Role of rapidly activating delayed rectifier K+ current in sinoatrial node pacemaker activity

Area of Science:

• Cardiovascular Physiology
• Electrophysiology
• Ion Channel Function

Background:

• The sinoatrial node (SAN) generates the heart's electrical impulse.
• Understanding ion channel contributions to SAN automaticity is vital for cardiac health.

Purpose of the Study:

• To investigate the role of the rapidly activating delayed rectifier potassium current (IK,r) in rabbit SAN cells.
• To characterize the electrophysiological effects of blocking IK,r on SAN action potentials.

Main Methods:

• Utilized the action potential clamp (AP clamp) technique with the selective IK,r blocker E-4031.
• Employed mathematical modeling to reconstruct IK,r kinetics based on whole-cell voltage-clamp data.
• Examined the impact of partial and complete IK,r block on spontaneously beating SAN cells.

Main Results:

• E-4031 application revealed a significant compensation current, maximal at -46.0 mV.
• IK,r block decreased action potential amplitude, maximum rate of rise, and repolarization rate.
• Complete IK,r block abolished spontaneous action potentials at -37.4 mV.

Conclusions:

• IK,r is essential for setting the maximum diastolic potential in SAN cells.
• IK,r ensures the reliable firing of subsequent action potentials in the SAN.
• This study highlights IK,r as a key determinant of cardiac automaticity.