Effect of antipsychotic drug perphenazine on fast sodium current and transient outward potassium current in rat ventricular myocytes
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Antipsychotic Agents administration & dosage toxicity MeSH
- Potassium Channels drug effects metabolism MeSH
- Inhibitory Concentration 50 MeSH
- Myocytes, Cardiac drug effects metabolism MeSH
- Rats MeSH
- Patch-Clamp Techniques MeSH
- Perphenazine administration & dosage toxicity MeSH
- Computer Simulation MeSH
- Rats, Wistar MeSH
- Sodium Channels drug effects metabolism MeSH
- Heart Ventricles cytology drug effects 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
- Antipsychotic Agents MeSH
- Potassium Channels MeSH
- Perphenazine MeSH
- Sodium Channels MeSH
Antipsychotic drug perphenazine belongs to the phenothiazine group commonly reported to induce ECG changes and tachyarrhythmias. Data about its effect on ionic membrane currents in cardiomyocytes are missing. We analyzed the effect of perphenazine (0.1-100 microM) on fast sodium current I (Na) and transient outward potassium current I (to) in enzymatically isolated rat right ventricular myocytes by the whole-cell patch-clamp technique at room temperature. Perphenazine reversibly blocked I (Na) (reducing its amplitude; IC(50) = 1.24 +/- 0.10 microM) and I (to) (accelerating its apparent inactivation with a slight decrease of its amplitude; IC(50) = 38.2 +/- 3.5 microM, evaluated from changes of the time integral). The fast time constant of I (to) inactivation was significantly decreased in a concentration-dependent manner (IC(50) = 30.0 +/- 6.6 microM). Both blocks were use and frequency dependent at 3.3 Hz. We conclude that perphenazine causes concentration-, use-, and frequency-dependent block of I (Na) and I (to) . Computer simulations suggest that perphenazine interacts preferentially with I (Na) channels in inactivated states and with I (to) channels in both open and open-inactivated states.
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