Sustained inward current during pacemaker depolarization in mammalian sinoatrial node cells

Area of Science:

• Cardiology
• Electrophysiology
• Molecular Biology

Background:

• Cardiac pacemaker cells possess multiple ion currents essential for action potential generation.
• Mathematical models show varying contributions of these currents to pacemaker activity.
• A novel sustained inward current (I(st)) was reported in rabbit sinoatrial node cells in 1995.

Purpose of the Study:

• To investigate the properties and role of the sustained inward current (I(st)) in cardiac automaticity.
• To characterize the novel current in sinoatrial (SA) and atrioventricular (AV) node cells.
• To determine the contribution of I(st) to the generation of spontaneous action potentials.

Main Methods:

• Electrophysiological recordings in sinoatrial (SA) and atrioventricular (AV) node cells.
• Single-channel analysis to characterize ionic conductance and gating kinetics.
• Patch-clamp techniques to study voltage-dependent currents and their inactivation properties.

Main Results:

• A sustained inward current (I(st)), showing minimal inactivation, was identified in SA node cells.
• Similar currents were found in SA and AV node cells of various species (rabbit, guinea pig, rat).
• Single-channel analysis revealed a nicardipine-sensitive Na(+) current with unique conductance and gating kinetics, distinct from other known channels.

Conclusions:

• The sustained inward current (I(st)) plays a significant role in the intrinsic automaticity of cardiac pacemaker cells.
• The identified Na(+) current is a key contributor to the slow diastolic depolarization phase.
• I(st) is essential for the generation of spontaneous action potentials in the SA and AV nodes.