Haloperidol prolongs diastolic phase of Ca(2+) transient in cardiac myocytes

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H Ishida1, K Hoshiai, M Hoshiai

  • 1Department of Physiology, School of Medicine, Tokai University, Isehara, 259-1193, Japan. ishida@is.icc.u-tokai.ac.jp.

The Japanese Journal of Physiology
|December 22, 1999
PubMed

Insights

Haloperidol (HPL) disrupts cardiac calcium handling, causing delayed afterdepolarizations and ventricular arrhythmias. This occurs through sarcoplasmic reticulum calcium release, independent of HPL's antipsychotic effects.

Area of Science:

  • Cardiology
  • Pharmacology
  • Molecular Biology

Background:

  • Haloperidol (HPL) is an antipsychotic drug linked to serious ventricular arrhythmias.
  • The precise mechanism of HPL-induced cardiotoxicity remains unclear.
  • Cardiac calcium ([Ca2+]i) homeostasis is critical for normal heart rhythm.

Purpose of the Study:

  • To investigate the effects of Haloperidol on intracellular calcium transients in cardiac myocytes.
  • To elucidate the role of calcium homeostasis abnormalities in HPL-induced arrhythmias.
  • To explore the underlying pathways of HPL's arrhythmogenic action.

Main Methods:

  • Cultured cardiac myocytes were used to examine Haloperidol's effects.
  • Intracellular calcium ([Ca2+]i) transients and cell motion were measured.
  • Mechanisms of calcium release from the sarcoplasmic reticulum were investigated.

Main Results:

  • Haloperidol prolonged the diastolic phase of the cardiac calcium transient.
  • A mid-diastolic re-elevation of intracellular calcium ([Ca2+]i) was observed.
  • This calcium re-elevation originated from sarcoplasmic reticulum release, triggering delayed afterdepolarizations and cell re-contraction.

Conclusions:

  • Haloperidol induces ventricular arrhythmias by disrupting cardiac calcium ([Ca2+]i) homeostasis.
  • Sarcoplasmic reticulum calcium release and subsequent delayed afterdepolarizations are key arrhythmogenic mechanisms.
  • The cardiotoxic effects of Haloperidol appear independent of its antipsychotic mechanism of action.

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