Abstract
1. Inhibition by haloperidol and chlorpromazine of a voltage-activated K+ current was characterized in rat phaeochromocytoma PC12 cells by use of whole-cell voltage-clamp techniques. 2. Haloperidol or chlorpromazine (1 and 10 microM) inhibited a K+ current activated by a test potential of +20 mV applied from a holding potential of -60 mV. The K+ current inhibition did not exhibit voltage-dependence when test potentials were changed between -10 and +40 mV or when holding potentials were changed between -120 and -60 mV. 3. Effects of compounds that are related to haloperidol and chlorpromazine in their pharmacological actions were examined. Fluspirilene (1 and 10 microM), an antipsychotic drug, inhibited the K+ current, but pimozide (1 and 10 microM), another antipsychotic drug did not significantly inhibit the K+ current. Sulpiride (1 or 10 microM), an antagonist of dopamine D2 receptors, did not affect the K+ current whereas (+)-SCH-23390 (10 microM), an antagonist of dopamine D1 receptors, reduced the K+ current. As for calmodulin antagonists, W-7 (100 microM), but not calmidazolium (1 microM), reduced the K+ current. 4. The inhibition by haloperidol or chlorpromazine of the K+ current was abolished when GTP in intracellular s...Continue Reading
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