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

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.

• Authors: Yue Lin, Yuanyuan Zhang, Qiongtao Song, Tao Song, Xue Han, Ying Zhang, Xuan Zhang, Xi Chu, Fenghua Zhang, Li Chu, Jianping Zhang
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 40 Issue 10 Pg. 1135-1145 (Oct 2017) ISSN: 1976-3786 [Electronic] Korea (South)
• PMID: 28766238 (Publication Type: Journal Article)

Chemical References

• 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

Topics

• 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, metabolism)
• Patch-Clamp Techniques
• Rats, Sprague-Dawley
• Saponins (pharmacology)
• Triterpenes (pharmacology)