Isoliensinine Eliminates Afterdepolarizations Through Inhibiting Late Sodium Current and L-Type Calcium Current

Cardiovasc Toxicol. 2021 Jan;21(1):67-78. doi: 10.1007/s12012-020-09597-z. Epub 2020 Aug 8.

Abstract

Isoliensinine (IL) extracted from lotus seed has a good therapeutic effect on cardiovascular diseases. However, its effect on ion channels of ventricular myocytes is still unclear. We used whole-cell patch-clamp techniques to detect the effects of IL on transmembrane ion currents and action potential (AP) in isolated rabbit left ventricular myocytes. IL inhibited the transient sodium current (INaT), late sodium current (INaL) enlarged by sea anemone toxin (ATX II) and L-type calcium current (ICaL) in a concentration-dependent manner without affecting inward rectifier potassium current (IK1) and delayed rectifier potassium current (IK). These inhibitory effects are mainly manifested as reduced the AP amplitude (APA) and maximum depolarization velocity (Vmax) and shortened the action potential duration (APD), but had no significant effect on the resting membrane potential (RMP). Moreover, IL significantly eliminated ATX II-induced early afterdepolarizations (EADs) and high extracellular calcium-induced delayed afterdepolarizations (DADs). These results revealed that IL effectively eliminated EADs and DADs through inhibiting INaL and ICaL in ventricular myocytes, which indicates it has potential antiarrhythmic action.

Keywords: Delayed afterdepolarizations; Early afterdepolarizations; Isoliensinine; L-type calcium current; Late sodium current.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects*
  • Animals
  • Anti-Arrhythmia Agents / pharmacology*
  • Arrhythmias, Cardiac / metabolism
  • Arrhythmias, Cardiac / physiopathology
  • Arrhythmias, Cardiac / prevention & control*
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels, L-Type / drug effects*
  • Calcium Channels, L-Type / metabolism
  • Female
  • Heart Rate / drug effects
  • Isoquinolines / pharmacology*
  • Male
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Rabbits
  • Sodium Channel Blockers / pharmacology*
  • Sodium Channels / drug effects*
  • Sodium Channels / metabolism
  • Time Factors

Substances

  • Anti-Arrhythmia Agents
  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Isoquinolines
  • Sodium Channel Blockers
  • Sodium Channels
  • isoliensinine