Effect of ajmaline on action potential and ionic currents in rat ventricular myocytes
Language English Country Slovakia Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
16308426
Knihovny.cz E-resources
- MeSH
- Adenosine Triphosphate chemistry MeSH
- Ajmaline pharmacology MeSH
- Action Potentials drug effects MeSH
- Anti-Arrhythmia Agents pharmacology MeSH
- Time Factors MeSH
- Models, Chemical MeSH
- Potassium chemistry MeSH
- Electrophysiology MeSH
- Inhibitory Concentration 50 MeSH
- Ions MeSH
- Rats MeSH
- Patch-Clamp Techniques MeSH
- Rats, Wistar MeSH
- Sodium chemistry MeSH
- Heart Ventricles drug effects MeSH
- Muscle Cells drug effects MeSH
- Temperature MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Adenosine Triphosphate MeSH
- Ajmaline MeSH
- Anti-Arrhythmia Agents MeSH
- Potassium MeSH
- Ions MeSH
- Sodium MeSH
The effect of ajmaline on action potential (AP) and ionic current components has been investigated in right ventricular myocytes of rat at room temperature using the whole cell patch clamp technique. Ajmaline decreased the upstroke velocity ((dV/dt)max) of AP and the AP amplitude, increased the AP duration measured at 50 and 90% repolarization, and reversibly inhibited most components of membrane ionic current in a concentration-dependent manner. The following values of IC50 and of the Hill coefficient (nH) resulted from approximation of the measured data by the Hill formula: for fast sodium current (INa) IC50=27.8+/-1.14 micromol/l and nH=1.27+/-0.25 at holding potential -75 mV, IC50=47.2+/-1.16 micromol/l and nH=1.16+/-0.21 at holding potential -120 mV; for L-type calcium current (ICa-L) IC50=70.8+/-0.09 micromol/l and n(H)=0.99+/-0.09; for transient outward potassium current (Ito) IC50=25.9+/-2.91 micromol/l and nH=1.07+/-0.15; for ATP-sensitive potassium current (IK(ATP)) IC50=13.3+/-1.1 micromol/l and nH=1.16+/-0.15. The current measured at the end of 300 ms depolarizing impulse was composed of an ajmaline-insensitive component and a component inhibited with IC50=61.0+/-1.1 micromol/l and nH=0.91+/-0.08. At hyperpolarizing voltages, ajmaline at high concentration of 300 micromol/l reduced the inward moiety of time-independent potassium current (IK1) by 36%. The results indicate that the inhibition of INa causes both the decreased rate of rise of depolarizing phase and the lowered amplitude of AP. The inhibition of Ito is responsible for the ajmaline-induced AP prolongation.