Inhibition by antipsychotic drugs of L-type Ca²⁺ channel current in PC12 cells

Inhibition by antipsychotic drugs of voltage-gated L-type Ca²⁺ channels was characterized in rat neuronal cell line pheochromocytoma PC12 cells. Under whole-cell voltage-clamp, haloperidol and chlorpromazine (1-100 μM) inhibited Ba²⁺ current permeating through Ca²⁺ channels. Fluspirilene and pimozide inhibited the Ba²⁺ current at lower concentrations (fluspirilene, 0.1 pM to 1 nM; pimozide 10 pM to 1 μM). Effects of dopamine receptor antagonists and calmodulin antagonists were tested because antipsychotic drugs are known to exhibit these pharmacological activities. Sulpiride (1 and 10 μM), an antagonist to dopamine D₂ receptors, and SCH-23390 (R(±)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-be nzazepine; 1 and 10 μM), an antagonist to dopamine D₁ receptors, also inhibited the Ba²⁺ current. As for calmodulin antagonists, W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide; 10 and 100 μM) as well as calmidazolium (10 nM to 1 μM) reduced the Ba²⁺ current. The inhibition by haloperidol or fluspirilene of the Ba²⁺ current was not affected when CTP in intracellular solution was replaced with GDPβS. These properties of the Ca²⁺ channel inhibition are discussed by comparing with those of the K⁺ channel inhibition and in relation to therapeutic relevance.