To the Mechanism of the Antiarrhythmic Action of Compound ALM-802: the Role of Ryanodine Receptors

Bull Exp Biol Med. 2023 Apr;174(6):734-737. doi: 10.1007/s10517-023-05781-7. Epub 2023 May 12.

Abstract

The effect of the compound N1-(2,3,4-trimethoxy)-N2-{2-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,2-ethane-diamine (code ALM-802) on the amplitude of the Ca2+ response in the cell was studied in in vitro experiments. The concentration of intracellular calcium was assessed using a Fura-2 two-wave probe. The experiments were performed on a culture of isolated rat hippocampal neurons. The effect of compound ALM-802 on the activity of ryanodine receptors (RyR2) was studied on an isolated strip of rat myocardium. The compound ALM-802 (69.8 μM) in hippocampal neurons causes a significant decrease in the amplitude of the Ca2+ response induced by addition of KCl to the medium. Experiments performed on an isolated myocardial strip showed that compound ALM-802 (10-5 M) almost completely blocked the positive inotropic reaction of the strip to the RyR2 agonist caffeine (5×10-5 M). The data obtained indicate that the decrease in the concentration of Ca2+ ions in the cell caused by ALM-802 is due to its ability to block RyR2 located on the membrane of the sarcoplasmic reticulum, which can be associated with the antiarrhythmic activity of the compound.

Keywords: Ca2+ ions; compound ALM-802; hippocampal neurons; isolated myocardial strip; ryanodine receptors.

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents / pharmacology
  • Caffeine / pharmacology
  • Calcium / metabolism
  • Myocardium* / metabolism
  • Rats
  • Ryanodine / metabolism
  • Ryanodine / pharmacology
  • Ryanodine Receptor Calcium Release Channel* / metabolism
  • Sarcoplasmic Reticulum

Substances

  • Ryanodine Receptor Calcium Release Channel
  • Anti-Arrhythmia Agents
  • Caffeine
  • Calcium
  • Ryanodine