Haloperidol depresses cardiac action potential by modulating multiple voltage-dependent ion channels
| Authors | |
|---|---|
| Year of publication | 2006 |
| Type | Article in Proceedings |
| Conference | France – New EU members New Frontiers in Cardiovascular Research:Subcellular mechanisms of altered muscle function in cardiovascular diseases |
| MU Faculty or unit | |
| Citation | |
| Field | Physiology |
| Keywords | cardiac action potential; haloperidol; patch-clamp |
| Description | Intravenous haloperidol is widely used as a treatment for delusional agitation in critically ill patients. However, life-threatening ventricular tachyarrhythmias are often associated with this therapy. Mechanisms by which the drug causes cardiac side effects have not been widely studied. We have investigated effects of haloperidol on excitability of myocytes freshly isolated from left ventricles of rat. Whole cell patch clamp method was employed. Haloperidol inhibited calcium, sodium and potassium currents in a dose-dependent manner. Moderate inhibition of Ito and IK,end current at the end of 250 ms long pulse in rat cardiomyocytes was reported previously (Nováková et al., Physiol. Research 54: 39P, 2005). We have observed inhibition of 39% of INa, and 19.5% of ICa when clinically relevant concentration of 1 umol/l was used. Dose dependence of the inhibition of voltage-dependent calcium current saturated at 26.5% of current amplitude reached at 10 umol/l. It was characterised by two IC50s of 2 nmol/l (block of 8% of current amplitude) and 2.4 umol/l (block of additional 18.5% of current amplitude). In current clamp recordings 10 umol/l fully suppressed action potential, foremost due to considerable suppression of INa. In contrast to our expectations, lower concentration of 1 umol/l caused moderate and reversible shortening of action potential duration. Effect of haloperidol on action potential shape is critically dependent on relative ratio of individual ionic currents and therefore may be highly species-dependent. Analysis of mechanism underlying haloperidol side effects must include analysis of all types of ion channels present in cardiomyocytes. |