Inotropic effects of MCI-154 on rat cardiac myocytes.
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.
Chen
Huan-Zhen
HZ
Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
Cui
Xiang-Li
XL
Zhao
Hua-Chen
HC
Zhao
Lu-Ying
LY
Lu
Ji-Yuan
JY
Wu
Bo-Wei
BW
D000818:Animals; D002118:Calcium / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002469:Cell Separation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000166:cytology; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019831:Sodium-Calcium Exchanger / Q000187:drug effects / Q000502:physiology
D020746:Calcium Channels, L-Type; D002316:Cardiotonic Agents; D011724:Pyridazines; D019831:Sodium-Calcium Exchanger; C052228:MCI 154; D002118:Calcium