Heterogeneity of effects of antipsychotic drugs on voltage-gated calcium channels type 2 (CaV2.2) currents

BARTOLOTTO, EMMANUEL E; MCCARTHY, CLARA I; CORDISCO GONZALEZ, SANTIAGO; MUSTAFÁ, EMILIO ROMÁN; RODRÍGUEZ, SILVIA SUSANA; RAINGO, JESICA

Villa Carlos Paz

Congreso; XXXIV Congress of the Argentine Society for Research in Neuroscience; 2019

Sociedad Argentina de investigación en Neurociencias

Antipsychotic (APs) are a heterogeneous group of drugs widely used in the treatment of schizophrenia (SCZ), but the molecular basis of their effects in neurons are not fully understood. CaV family is critical for controlling calcium influx in neurons, thus modulating transcription (CaV1), neurotransmission (CaV2) and electrical activity (CaV3). Moreover, localization, genetic variations and function of CaV are associated with SCZ and some APs function as CaV1 and CaV3 blockers. In this work, we evaluated the effects of three different APs on CaV2.2 currents. We selected two typical (haloperidol and chlorpromazine) and one atypical (risperidone) APs with different chemical structures and diverse physiological effects. We transfected HEK293T cells with CaV2.2 and its auxiliary subunits and recorded calcium currents by voltage clamp. We evaluated the effect of increasing concentrations of APs on CaV2.2 current levels. We performed dose-response curves for each AP and found dissimilar effects. Haloperidol and risperidone acutely inhibited CaV2.2 currents. However, CaV2.2 currents were considerably more sensitive to haloperidol compared to risperidone. On the contrast, chlorpromazine showed no effect on CaV2.2 currents. These and future experiments will allow us to understand the role of calcium channel modulation by APs related to the high diversity of neuronal effects shown by these drugs.