The L-type voltage-gated calcium channel modulates microglial pro-inflammatory activity

• Published in: Molecular and cellular neuroscience Vol. 64; pp. 104 - 115
• Main Authors: Espinosa-Parrilla, J.F., Martínez-Moreno, M., Gasull, X., Mahy, N., Rodríguez, M.J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2015; Elsevier B.V
• Subjects: Animals; Calcium channels; Calcium Channels, L-Type - genetics; Calcium Channels, L-Type - metabolism; Canals de calci; Cell Line; Central nervous system; Dihydropyridine receptor; Excitotoxicity; Hippocampus - cytology; Hippocampus - metabolism; L-type voltage-gated calcium channel; Malalties neurodegeneratives; Male; Mice; Microglia; Microglia - metabolism; Micròglia; Neurodegeneration; Neurodegenerative diseases; Neuroinflammation; Nitric Oxide - metabolism; Phagocytosis; Rats; Rats, Wistar; Sistema nerviós central; Tumor Necrosis Factor-alpha - metabolism; IFNγ; PBS; DG; [Ca2+]i; DAB; Dihydropyridine receptor; Neuroinflammation; IL-1β; KW; LPS; GFAP; TNF-α; Neurodegeneration; FBS; Excitotoxicity; MDP; NMDA; L-type voltage-gated calcium channel; IB4; SEM; NGS; LSD
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1016/j.mcn.2014.12.004

Under pathological conditions, microglia, the resident CNS immune cells, become reactive and release pro-inflammatory cytokines and neurotoxic factors. We investigated whether this phenotypic switch includes changes in the expression of the L-type voltage-gated calcium channel (VGCC) in a rat model of N-methyl-d-aspartate-induced hippocampal neurodegeneration. Double immunohistochemistry and confocal microscopy evidenced that activated microglia express the L-type VGCC. We then analyzed whether BV2 microglia express functional L-type VGCC, and investigated the latter's role in microglial cytokine release and phagocytic capacity. Activated BV2 microglia express the CaV1.2 and CaV1.3 subunits of the L-type VGCC determined by reverse transcription-polymerase chain reaction, Western blot and immunocytochemistry. Depolarization with KCl induced a Ca2+ entry facilitated by Bay k8644 and partially blocked with nifedipine, which also reduced TNF-α and NO release by 40%. However, no nifedipine effect on BV2 microglia viability or phagocytic capacity was observed. Our results suggest that in CNS inflammatory processes, the L-type VGCC plays a specific role in the control of microglial secretory activity.
•Reactive microglial from hippocampus express α1 subunits of the L-type VGCC in vivo and in vitro.•Nifedipine and Bay k8644 modulate intracellular calcium concentration of reactive BV2 microglia.•L-type VGCC participates in the control of the pro-inflammatory activity of microglia.