Ionic currents responsible for the generation of pace-maker current in the rabbit sino-atrial node

Area of Science:

• Cardiovascular Physiology
• Electrophysiology
• Cellular Biology

Background:

• The sino-atrial node (SAN) is the heart's natural pacemaker.
• Understanding the ionic basis of the pacemaker current (delta Ip, If, Ih) is crucial for comprehending heart rate regulation.

Purpose of the Study:

• To investigate the ionic nature of the pacemaker current (delta Ip) in rabbit sino-atrial node cells.
• To determine the roles of sodium (Na+), calcium (Ca2+), and potassium (K+) ions in generating the pacemaker potential.

Main Methods:

• Single sucrose-gap voltage-clamp technique applied to rabbit sino-atrial node cells.
• Ionic manipulations including tetrodotoxin, Ca2+-channel blockers, removal of extracellular Na+ and Ca2+, and application of Cs+, Ba2+, and tetraethylammonium.
• Double-pulse procedure to assess time-dependent current components.

Main Results:

• Tetrodotoxin did not affect the primary pacemaker current or potential, but a tetrodotoxin-sensitive channel was activated by hyperpolarization.
• Ca2+-channel blockers and Ca2+ removal had minimal impact on delta Ip voltage dependence and pacemaker potential range.
• Removal of Na+ completely suppressed delta Ip and caused hyperpolarization, suggesting Na+ as the primary charge carrier.
• Low concentrations of Cs+ markedly suppressed delta Ip activation and reduced pacing rate, while Ba2+ and tetraethylammonium had no significant effect.
• A time-dependent component of delta Ip, reversing near the K+ equilibrium potential (EK), was observed in some experiments.

Conclusions:

• The pacemaker current (delta Ip) in rabbit SAN cells is primarily carried by Na+ ions.
• Cs+ ions act as a potent blocker of the pacemaker current.
• While Na+ is the main carrier, Ca2+ likely influences pacing rate through modulation of K+ conductance, in addition to its role in the Isi system.