Haloperidol Prolongs Diastolic Phase of Ca〔2+〕Transientin Cardiac Myocytes

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  • Haloperidol Prolongs Diastolic Phase of Ca2+ Transient in Cardiac Myocytes.

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Haloperidol (HPL), a widely used antipsychotic drug, is known to induce serious ventricular arrhythmias. However, the mechanism underlying their induction is not clear. We therefore examined the effects of HPL on the intracellular Ca2+ ([Ca2+]i) transient and on cell motion in cultured cardiac myocytes, as well as the pathways involving the HPL-induced abnormality of Ca2+ homeostasis. HPL prolonged the diastolic phase of the Ca2+ transient, with 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 factor. The re-elevation of [Ca2+]i coincided with cell re-contraction during diastole. The induction of this abnormality by HPL appears to be independent of the mechanisms of the antipsychotic action.<br>

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