Haloperidol prolongs diastolic phase of Ca2+ transient in cardiac myocytes

Haloperidol (HPL), a widely used antipsychotic drug, is known to induce ser ious ventricular arrhythmias. However, the mechanism underlying their induc tion is not clear. We therefore examined the effects of HPL on the intracel lular Ca2+ ([Ca2+](i)) transient and on cell motion in cultured cardiac myo cytes, as well as the pathways involving the HPL-induced abnormality of Ca2 + homeostasis. HPL prolonged the diastolic phase of the Ca2+ transient, wit h a mid-diastolic re-elevation of [Ca2+](i). The re-elevation of [Ca2+](i) was:shown to be provoked by Ca2+ release from sarcoplasmic reticulum (SR), which can trigger delayed afterdepolarization, the major arrhythmogenic fac tor. The re-elevation of [Ca2+]i coincided with:cell re-contraction during diastole. The induction of this abnormality by HPL appears to be independen t of the mechanisms of the antipsychotic action.