[Testosterone modulation of HERG potassium channel blockade induced by neuroleptics].

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.

[Effects of sex hormones on HERG potassium channels expressed in Xenopus oocytes].

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 effects of testosterone and 17 beta-estradiol on HERG-encoded K+ channels, expressed in Xenopus oocytes. At 1M concentration testosterone decreased the amplitude of HERG-directed IKr (rapid component of cardiac delayed rectifier K+ current) by 30% within 30 min of exposure, while 17-estradiol had no effect.

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