Constitutive activity of the dopamine (D5) receptor, highly expressed in CA1 hippocampal neurons, selectively reduces CaV3.2 and CaV3.3 currents

• DOI: 10.1111/bph.16006
• Publication Date: 2022-12-08T15:56:34Z
• Authors: Emilio Román Mustafá; Clara Inés McCarthy; Andrea Estefanía ...; Santiago Cordisco...; Silvia Susana Rod...; Jesica Raingo
• Keywords: HEK 293 cells; Inverse agonist; Calcium imaging

Background and Purpose Ca V 3.1‐3 currents differentially contribute to neuronal firing patterns. 3 are regulated by G protein‐coupled receptors (GPCRs) activity, but information about as targets of the constitutive activity GPCRs is scarce. We investigate impact D 5 recpetor a GPCR with high levels basal on functionality. expressed in hippocampus have been independently linked pathophysiological states associated epilepsy. Experimental Approach Our study models were HEK293T cells heterologously expressing 1 or receptor 3.1‐3, mouse brain slices containing hippocampus. used chlorpromazine (D /D inverse agonist) mutant lacking experimental tools. measured excitability parameters using patch‐clamp technique. completed our computational modelling imaging Key Results found higher sensitivity TTA‐P2 (Ca blocker) CA1 pyramidal neurons obtained from chlorpromazine‐treated animals compared vehicle‐treated animals. that 3.2 3.3—but not 3.1—are cells. Finally, we an increased rate comparison Similar changes observed model controlled levels. Conclusions Implications Native hippocampal recombinant 3.2‐3 sensitive activity. Manipulation could be valuable strategy control excitability, especially exacerbated conditions such