Perphenazine-Induced block of sodium and transient outward potassium current: experimental and simulation study

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Authors

BÉBAROVÁ Markéta MATEJOVIČ Peter PÁSEK Michal JANSOVÁ Dagmar ŠIMURDOVÁ Milena NOVÁKOVÁ Marie ŠIMURDA Jiří

Year of publication 2008
Type Article in Periodical
Magazine / Source Analysis of Biomedical Signals and Images
MU Faculty or unit

Faculty of Medicine

Citation
Field Physiology
Keywords sodium current;potassium outward current;simulation
Description The effect of a neuroleptic drug perphenazine on sodium current INa and transient outward potassium current Ito was studied in rat ventricular myocytes at room temperature. Perphenazine reversibly blocked INa (reducing its amplitude; IC50 = 1.24+/-0.10 micromol/l, nH = 0.99+/-0.08) and Ito (accelerating its apparent inactivation with a slight decrease of its amplitude; IC50 = 38.2+/-3.5 micromol/l, nH = 0.75+/-0.07, evaluated from the changes of time integral). Both INa- and Ito-block was use- and frequency-dependent (20%-increase of INablock and 10%-increase of Ito-block under 0.3 and 10 micromol/l perphenazine, respectively, at the stimulation frequency of 3.3 Hz applied after a 15-s rest). The results of quantitative modelling suggest that perphenazine interacts with INa-channels in inactivated states, and with Ito-channels in both open and open-inactivated states.
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