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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(3): 11-18


Testosteron modulationof herg channels block by neuroleptics

V.E.degtiar, V.N.osipenko, Y.M.shuba

    A. A. Bogomoletz Institute of Physiology, and International Center of MolecularPhysiology National Academy of Sciences of Ukraine, Kiev, Ukraine


Abstract

The repolarisation phase of cardiac action potential is characterized by sexual dimorphism suggesting the role of sex steroid hormones in the regulation of K+ channels. Here we report on the effect of testosterone on blockade of HERG-encoded K+ channels induced by neuroleptics. These compounds 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. HERG was expressed in Xenopus oocytes, HERG-expressing oocytes were preincubated in 1 mM of testosteron from 3 to 8 hours before experiments. The extent of the blockade by neuroleptics in control oocytes increased with depolarization correlating with channels activation consistent with open-channel blocking mechanism. The ?N50 and A (maximal block) values for the haloperidol-, pimozide- and fluspirileninduced blockade of fully activated IKr were 1,36 mM and 73 %, 1,74 mM and 76 %, 2,34 mM and 65 % respectively. Testosteron decreased extent of maximal block and significantly diminished block voltage-dependance of IKr inhibition, it also decreased the efficiency of block, with ?N50 and A values of 2,73 mM and 65 %, 2,08 mM and 59 %, 5,04 mM and 64 % for haloperidol, pimozide and fluspirilen respectively. Testosteron treatment increased ?N50 and decreased A for all three agents. The largest decrease in A was with pimozide and the largest increase in ?N50 was with fluspirilen. Our results suggest protective role of testosteron (androgens) against proarrhythmic side effects of some compounds.

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