Blockade of HERG K+ channels expressed in Xenopus oocytes by antipsychotic agents].

V M Osypenko, V Ie Degtiar, V G Naid'onov, Ia M Shuba

A. A. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine.

Fiziolohichnyĭ zhurnal (Kiev, Ukraine : 1994) 2001

filter terms:

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.

Citation

V M Osypenko, V Ie Degtiar, V G Naid'onov, Ia M Shuba. Blockade of HERG K+ channels expressed in Xenopus oocytes by antipsychotic agents]. Fiziolohichnyĭ zhurnal (Kiev, Ukraine : 1994). 2001;47(1):17-25