Ketamine and Sodium Selenite Promote Transient Receptor Potential Vanilloid 1-Associated Calcium Signaling and Apoptosis in SH-SY5Y Neuroblastoma Cells.

Abstract

Ketamine has pharmacological actions beyond N-methyl-D-aspartate receptor antagonism, whereas sodium selenite modulates redox-dependent signaling. Transient receptor potential vanilloid 1 (TRPV1) channels regulate Ca²⁺ influx and may contribute to oxidative stress-associated apoptosis. We investigated whether ketamine and sodium selenite, alone and combined, promote apoptosis through TRPV1-associated mechanisms in SH-SY5Y neuroblastoma cells. Cells were assigned to control, ketamine+sodium selenite (Ket+Sel), Ket+Sel+capsazepine (CPZ), ketamine, ketamine+CPZ, sodium selenite, and sodium selenite+CPZ groups. Ketamine (10 µM) and/or sodium selenite (500 nM) were applied for 48 h; CPZ (0.1 mM, 30 min) was used for pharmacological antagonism, and capsaicin (0.1 mM) for stimulation. Intracellular Ca²⁺ responses were assessed using Fura-2-AM, whereas apoptosis, reactive oxygen species production, mitochondrial depolarization, and caspase-3/9 activities were measured spectrophotometrically or fluorometrically. Under capsaicin-stimulated assay conditions, ketamine and sodium selenite increased all endpoints relative to control, and the combined treatment produced the greatest responses for most endpoints. CPZ attenuated Ca²⁺ responses and several downstream oxidative and apoptotic markers. These findings indicate that ketamine and sodium selenite, particularly in combination, enhance apoptosis through a CPZ-sensitive pathway compatible with TRPV1-associated Ca²⁺-ROS-mitochondrial signaling, while not establishing exclusive TRPV1 mediation.

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