Electrophysiologic effects of lercanidipine on repolarizing potassium currents.

Blockade of cardiac repolarizing potassium channels by drugs may result in QT-interval prolongation, eventually degenerating into "torsades de pointes," a life-threatening arrhythmia. Lercanidipine (LER) is a recently introduced lipophilic calcium antagonist with no cardiodepressant activity and long-lasting antihypertensive action. Its chemical structure is characterized by the presence of a diphenylpropylaminoalkyl group, which is present in some of the drugs that have been reported to cause QT-interval prolongation. Our previous data demonstrated that LER blocks L-type calcium channels without affecting sodium current; however, no data an available concerning its effects on cardiac potassium channels. Transient outward (I-to), delayed rectifier (I-K), background currents, and action potential (AP) profile were measured from patch-clamped ventricular myocytes isolated from rat, guinea pig, or human hearts using enzymatic dissociation procedures. LER did not affect I-K (and I-Kr) density and activation curve in guinea pig myocytes; the reversal potential of the background current (I-KI) and its slope were not changed by the drug. Maximal diastolic potential (MDP) and duration of the AP measured at -60 mV (APD(-60)) were not significantly changed. I-to density and activation curves measured in rat myocytes were similar in the absence and presence of 1 or 10 muM LER. Finally, the effect of LER was tested in human ventricular myocytes: superfusion with 1 muM LER did not affect MDP and APD(-60). I-to density and the midpoint of activation and inactivation curves were similar in the absence and presence of LER. In conclusion, our data demonstrate that LER does net affect repolarizing potassium currents and action potential profile recorded from guinea pig, rat, and human ventricular myocytes. It is unlikely that LER could cause QT prolongation in vivo.