Cesium effects on i(f) and i(K) in rabbit sinoatrial node myocytes: implications for SA node automaticity

Area of Science:

• Cardiology
• Electrophysiology
• Ion Channel Physiology

Background:

• The sinoatrial (SA) node generates the heart's electrical impulse.
• The hyperpolarization-activated current (i(f)) and delayed-rectifier current (i(K)) are key to SA node pacemaker potential.
• Cesium (Cs+) is known to block i(f) but its effect on SA node discharge is debated.

Purpose of the Study:

• To investigate the role of i(K) in SA node pacemaker potential.
• To determine if Cs+ resistance to blocking i(K) explains its incomplete effect on SA node discharge.
• To elucidate the combined effects of Cs+ on i(f) and i(K) in SA node cells.

Main Methods:

• Perforated patch-clamp technique on single SA node cells.
• Studied effects of 2 mM Cs+ on i(f) and i(K) at pacemaker potentials.
• Applied hyperpolarizing and depolarizing voltage steps to isolate and activate specific currents.

Main Results:

• Cs+ (2 mM) reversibly blocked i(f) and increased slope conductance, confirming i(f) predominance in pacemaker range.
• Cs+ significantly reduced i(f) but only slightly decreased i(K).
• SA node discharge was not blocked by Cs+, suggesting i(K) plays a crucial role.

Conclusions:

• The failure of Cs+ to block SA node discharge is not due to incomplete i(f) block or a shift in its activation range.
• The resistance of i(K) to Cs+ block indicates its predominant role in SA node pacing.
• Cs+ may slow SA node discharge by both suppressing i(f) and reducing i(K).