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Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
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ICaL and Ito mediate rate-dependent repolarization in rabbit atrial myocytes

Jian-Wen Hou1, Wei Li1, Yu-Dong Fei1

  • 1Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, Shanghai, 200092, China.

Journal of Physiology and Biochemistry
|December 16, 2017
PubMed

Insights

Rate-dependent repolarization (RDR) in rabbit atrial cells is primarily mediated by transient outward potassium current (Ito) and L-type calcium current (ICaL). The late sodium current (INaL) plays a negligible role in this process.

Area of Science:

  • Cardiovascular Physiology
  • Electrophysiology
  • Cardiac Electrophysiology

Background:

  • Rate-dependent repolarization (RDR) of cardiomyocyte action potentials (APs) is crucial for cardiac rhythm. Atrial RDR is implicated in atrial fibrillation pathogenesis.
  • Studies on RDR mechanisms in rabbit atria are limited, necessitating further investigation into underlying cellular processes.

Purpose of the Study:

  • To elucidate the ionic mechanisms responsible for RDR in isolated rabbit atrial cells.
  • To determine the specific contributions of transient outward potassium current (Ito), L-type calcium current (ICaL), and late sodium current (INaL) to atrial RDR.

Main Methods:

  • Isolation of single atrial cells from rabbit hearts for electrophysiological recordings.
  • Pharmacological blockade of Ito using 4-Aminopyridine (4-AP) and ICaL using nifedipine.
  • Assessment of action potential duration (APD) at 20% (APD20), 50% (APD50), and 90% (APD90) repolarization under varying pacing rates.
  • Inhibition of late sodium current (INaL) using GS-458967 (GS967).

Main Results:

  • Rate-dependent prolongation was observed in APD20 and APD50, but not APD90, under control conditions.
  • 4-AP abolished APD20 and APD50 rate-dependence and unmasked rate-dependent APD90 reduction, which was attenuated by nifedipine.
  • GS967 showed minimal impact on APD90, indicating a negligible role for INaL in rabbit atrial RDR.
  • Ito and ICaL exhibited significant rate-dependent reductions due to slow reactivation kinetics, consistent with AP findings.

Conclusions:

  • Transient outward potassium current (Ito) and L-type calcium current (ICaL) are the primary determinants of rate-dependent repolarization in rabbit atrial cells.
  • The late sodium current (INaL) has a minimal contribution to the rate-dependent properties of action potentials in the rabbit atrium.
  • Understanding these ionic mechanisms is vital for insights into atrial electrophysiology and the development of antiarrhythmic strategies for conditions like atrial fibrillation.

Keywords:
Atrial myocytesL-type calcium currentLate sodium currentRate-dependent repolarizationTransient outward potassium current

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