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Inotropic effects of MCI-154 on rat cardiac myocytes.
- Source :
-
Sheng li xue bao : [Acta physiologica Sinica] [Sheng Li Xue Bao] 2004 Jun 25; Vol. 56 (3), pp. 301-5. - Publication Year :
- 2004
-
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.
- Subjects :
- Animals
Calcium Channels, L-Type drug effects
Calcium Signaling drug effects
Cell Separation
Cells, Cultured
Dose-Response Relationship, Drug
Heart Ventricles cytology
Myocardial Contraction drug effects
Myocytes, Cardiac cytology
Patch-Clamp Techniques
Rats
Rats, Wistar
Sodium-Calcium Exchanger drug effects
Sodium-Calcium Exchanger physiology
Calcium physiology
Cardiotonic Agents pharmacology
Myocytes, Cardiac metabolism
Pyridazines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0371-0874
- Volume :
- 56
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Sheng li xue bao : [Acta physiologica Sinica]
- Publication Type :
- Academic Journal
- Accession number :
- 15224141