Expression and Pharmacology of Endogenous Cav Channels in SH-SY5Y Human Neuroblastoma Cells

摘要: SH-SY5Y human neuroblastoma cells provide a useful in vitro model to study the mechanisms underlying neurotransmission and nociception. These are derived from sympathetic neuronal tissue thus, express number of Cav channel subtypes essential for regulation important physiological functions, such as heart contraction nociception, including clinically validated pain target Cav2.2. We have detected mRNA transcripts range endogenous expressed Cav1.3, Cav2.2 (including two three splice variant isoforms) Cav3.1 cells; well auxiliary subunits α2δ1–3, β1, β3, β4, γ1, γ4–5, γ7. Both high- low-voltage activated channels generated calcium signals cells. Pharmacological characterisation using ω-conotoxins CVID MVIIA revealed significantly (∼ 10-fold) higher affinity at versus rat Cav2.2, while GVIA, which interacts with through distinct pharmacophore had similar both species. CVID, GVIA was membranes vs whole binding assays functional assays, suggesting endogenously native systems can strongly influence pharmacology. results may implications strategies used identify therapeutic leads channels.