Inotropic effects of MCI-154 on rat cardiac myocytes.
- Author:
Huan-Zhen CHEN
1
;
Xiang-Li CUI
;
Hua-Chen ZHAO
;
Lu-Ying ZHAO
;
Ji-Yuan LU
;
Bo-Wei WU
Author Information
1. Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Calcium;
physiology;
Calcium Channels, L-Type;
drug effects;
Calcium Signaling;
drug effects;
Cardiotonic Agents;
pharmacology;
Cell Separation;
Cells, Cultured;
Dose-Response Relationship, Drug;
Heart Ventricles;
cytology;
Myocardial Contraction;
drug effects;
Myocytes, Cardiac;
cytology;
metabolism;
Patch-Clamp Techniques;
Pyridazines;
pharmacology;
Rats;
Rats, Wistar;
Sodium-Calcium Exchanger;
drug effects;
physiology
- From:
Acta Physiologica Sinica
2004;56(3):301-305
- CountryChina
- Language:English
-
Abstract:
Calcium sensitizers exert positive inotropic effects without increasing intracellular Ca(2+). Thus, they avoid the undesired effects of Ca(2+) overload such as arrhythmias and cell injury, but most of them may impair myocyte relaxation. However, MCI-154, also a calcium sensitizer, has no impairment to cardiomyocyte relaxation. To clarify the underlying mechanisms, we examined the effects of MCI-154 on Ca(2+) transient and cell contraction using ion imaging system, and its influence on L-type Ca(2+) current and Na(+)/ Ca(2+) exchange current with patch clamp technique in rat ventricular myocytes as well. The results showed that: (1) MCI-154 (1-100 micromol/L) had no effect on L-type Ca(2+) current; (2) MCI-154 concentration-dependently increased cell shortening from 5.00+/-1.6 microm of control to 6.2+/-1.6 microm at 1 micromol/L, 8.7+/-1.6 microm at 10 micromol/L and 14.0+/-1.4 microm at 100 micromol/L, respectively, with a slight increase in Ca(2+) transient amplitude and an abbreviation of Ca(2+) transient restore kinetics assessed by time to 50% restore (TR(50)) and time to 90% restore (TR(90)); (3) MCI-154 dose-dependently increased the electrogenic Na(+)/ Ca(2+) exchange current both in the inward and the outward directions in rat ventricular myocytes. These results indicate that MCI-154 exerted a positive inotropic action without impairing myocyte relaxation. The stimulation of inward Na(+)/ Ca(2+) exchange current may accelerate the Ca(2+) efflux, leading to abbreviations of TR(50) and TR(90) in rat myocytes. The findings suggest that the improvement by MCI-154 of myocyte relaxation is attributed to the forward mode of Na(+)/ Ca(2+) exchange.
