Objective: We aimed to investigate the effects of chronic fluoxetine (a selective serotonin reuptake antidepressant inhibitor) treatment (10 mg/kg per os, daily for 6-8 weeks) on action potential (AP) characteristics of isolated right ventricular papillary muscles and left atria of streptozotocin-induced (60 m/kg iv.) diabetic and agematched control rats. Methods: A conventional glass microelectrode technique was used to record AP parameters.
Results: The duration of AP (APD) of diabetic ventricular as well as atrial muscles were significantly increased with no significant differences in the resting membrane potential and maximum rate of the rise of depolarization phase of AP (Vmax or dv/dt). Chronic fluoxetine treatment slightly, but not significantly decreased the action potential amplitude (APA) and Vmax both in control and diabetic groups but did not modify other parameters of APs. Conclusion: The electrophysiological changes found in diabetic heart preparations are mainly due to a decrease in outward K+ current (Ito), with a possible contribution of altered Ca2+ current(s). Some of these electrophysiological alterations may explain certain characteristic pathological ECG changes (T wave flattening or inversion, reentry arrhytmias) encountered frequently in diabetic patients. Fluoxetine seems to be a well tolerated, safe antidepressant in therapeutic doses even in high risk, diabetic patients, although a slight decrease found in APA and Vmax may indicate that this drug administered in higher doses can exert certain cardiodepressive effects.

Keywords: cardiac action potential, diabetes, fluoxetine, Rat