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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2001; 47(1): 17-25

The blockade of herg k+ channels expressedin xenopus oocytes by neuroleptic agents

V. N. Osipenko, V. E. Degtiar, V. G. Naidionov, Y. M. Shuba

    A. A. Bogomoletz Institute of PhysiologyNational Academy of Sciences of Ukraine;International Center of Molecular PhysiologyNational Academy of Sciences of Ukraine, Kiev



Abstract

V. N. Osipenko, V. E. Degtiar, V. G. Naidionov, Y. M. Shuba THE BLOCKADE OF HERG K+ CHANNELS EXPRESSED IN XENOPUS OOCYTES BY NEUROLEPTIC AGENTS 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 dalayed 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 ?N50 values for the haloperidol-, pimozide- and fluspirilen-induced blockade of fully activated IKr were 1.36, 1.74 and 2.34 mnM 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. A. A. Bogomoletz Institute of Physiology National Academy of Sciences of Ukraine; International Center of Molecular Physiology National Academy of Sciences of Ukraine, Kiev

Full text: (PDF, in Ukrainian)

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