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[Blockade of HERG K+ channels expressed in Xenopus oocytes by antipsychotic agents].
Fiziol Zh. 2001; 47(1):17-25.FZ

Abstract

We have investigated the effects of neuroleptic agents, haloperidol, pimozide and fluspirilen, that are used in clinics to treat psychiatric disorders, but reportedly have proarrhythmic side effects, on HERG-encoded K+ channels responsible for the rapid component of cardiac delayed rectifier K+ current, IKr. All three agents blocked HERG-directed IKr in Xenopus oocytes in a voltage-dependent manner. The extent of the blockade increased with depolarization correlating with channels activation consistent with open-channel blocking mechanism. The IC50 values for the haloperidol-, pimozide- and fluspirilen-induced blockade of fully activated IKr were 1.36, 1.74 and 2.34 mcM respectively. Neuroleptics did not affect the HERG channels steady-state activation and inactivation properties. Thus, the blockade of HERG channels may underly proarrhythmic actions of neuroleptics resulting in a slowing down of the repolarization phase of cardiac action potential, and prolongation of the electrocardiographic QT interval.

Authors+Show Affiliations

A. A. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
English Abstract
Journal Article

Language

ukr

PubMed ID

11296551

Citation

Osypenko, V M., et al. "[Blockade of HERG K+ Channels Expressed in Xenopus Oocytes By Antipsychotic Agents]." Fiziolohichnyi Zhurnal (Kiev, Ukraine : 1994), vol. 47, no. 1, 2001, pp. 17-25.
Osypenko VM, Degtiar VIe, Naid'onov VG, et al. [Blockade of HERG K+ channels expressed in Xenopus oocytes by antipsychotic agents]. Fiziol Zh. 2001;47(1):17-25.
Osypenko, V. M., Degtiar, V. I. e., Naid'onov, V. G., & Shuba, I. a. M. (2001). [Blockade of HERG K+ channels expressed in Xenopus oocytes by antipsychotic agents]. Fiziolohichnyi Zhurnal (Kiev, Ukraine : 1994), 47(1), 17-25.
Osypenko VM, et al. [Blockade of HERG K+ Channels Expressed in Xenopus Oocytes By Antipsychotic Agents]. Fiziol Zh. 2001;47(1):17-25. PubMed PMID: 11296551.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Blockade of HERG K+ channels expressed in Xenopus oocytes by antipsychotic agents]. AU - Osypenko,V M, AU - Degtiar,V Ie, AU - Naid'onov,V G, AU - Shuba,Ia M, PY - 2001/4/12/pubmed PY - 2002/6/19/medline PY - 2001/4/12/entrez SP - 17 EP - 25 JF - Fiziolohichnyi zhurnal (Kiev, Ukraine : 1994) JO - Fiziol Zh VL - 47 IS - 1 N2 - We have investigated the effects of neuroleptic agents, haloperidol, pimozide and fluspirilen, that are used in clinics to treat psychiatric disorders, but reportedly have proarrhythmic side effects, on HERG-encoded K+ channels responsible for the rapid component of cardiac delayed rectifier K+ current, IKr. All three agents blocked HERG-directed IKr in Xenopus oocytes in a voltage-dependent manner. The extent of the blockade increased with depolarization correlating with channels activation consistent with open-channel blocking mechanism. The IC50 values for the haloperidol-, pimozide- and fluspirilen-induced blockade of fully activated IKr were 1.36, 1.74 and 2.34 mcM respectively. Neuroleptics did not affect the HERG channels steady-state activation and inactivation properties. Thus, the blockade of HERG channels may underly proarrhythmic actions of neuroleptics resulting in a slowing down of the repolarization phase of cardiac action potential, and prolongation of the electrocardiographic QT interval. SN - 2522-9028 UR - https://www.unboundmedicine.com/medline/citation/11296551/[Blockade_of_HERG_K+_channels_expressed_in_Xenopus_oocytes_by_antipsychotic_agents]_ L2 - https://antibodies.cancer.gov/detail/CPTC-PIK3CA-1 DB - PRIME DP - Unbound Medicine ER -