Magnesium isoglycyrrhizinate inhibits L-type Ca2+ channels, Ca2+ transients, and contractility but not hERG K+ channels

Arch Pharm Res. 2017 Oct;40(10):1135-1145. doi: 10.1007/s12272-017-0938-6. Epub 2017 Aug 1.

Abstract

To explore the cardiovascular protective effects of Magnesium isoglycyrrhizinate (MI), especially the underlying cellular mechanisms related to L-type calcium channels and myocardial contractility, and to examine the effects of MI on hERG K+ current expressed in HEK293 cells. We used the whole-cell patch clamp technique, video-based edge detection and dual excitation fluorescence photomultiplier systems to explore the effect of MI on L-type Ca2+ currents (ICa-L) and cell contraction in rat cardiomyocytes. We also examined the rapidly activating delayed rectifier potassium current (IKr) expressed in HEK293 cells using a perforated patch clamp. MI inhibited ICa-L in a dose-dependent manner, with a half-maximal inhibitory concentration (IC50) of 0.22 mg/ml, and the maximal inhibitory effect was 61.10 ± 0.59%. MI at a concentration of 0.3 mg/ml reduced cell shortening by 24.12 ± 3.97% and the peak value of the Ca2+ transient by 36.54 ± 4.96%. MI had no significant influence on hERG K+ channels expressed in HEK293 cells at all test potentials. MI exerts protective effects on the heart via the inhibition of ICa-L and cell shortening in rat cardiomyocytes. However, MI had no significant influence on IKr; thus, MI may exert cardioprotective effects without causing drug-induced long QT syndrome.

Keywords: Ca2+ transient; L-type Ca2+ currents; Magnesium isoglycyrrhizinate; Myocyte shortening; Rat cardiomyocyte; hERG K+ channels.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels, L-Type / metabolism*
  • Cardiotonic Agents / pharmacology*
  • Cell Culture Techniques
  • Dose-Response Relationship, Drug
  • ERG1 Potassium Channel / antagonists & inhibitors*
  • HEK293 Cells
  • Humans
  • Membrane Potentials / drug effects
  • Myocardial Contraction / drug effects*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Patch-Clamp Techniques
  • Rats, Sprague-Dawley
  • Saponins / pharmacology*
  • Triterpenes / pharmacology*

Substances

  • 18alpha,20beta-hydroxy-11-oxo-norolean-12-en-3beta-yl-2-O-beta-D-glucopyranurosyl-alpha-D-glucopyranosiduronate magnesium tetrahydrate
  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Cardiotonic Agents
  • ERG1 Potassium Channel
  • KCNH2 protein, human
  • Saponins
  • Triterpenes
  • Calcium