Glutamate triggers intracellular Ca2+ oscillations and nitric oxide release by inducing NAADP ‐ and InsP3‐dependent Ca2+ release in mouse brain endothelial cells

Glutamate induces intracellular Ca2+ oscillations in mouse brain microvascular endothelial cells. Glutamate ‐induced intracellular Ca2+ oscillations lead to robust, although delayed, nitric oxide release. Brain microvascular endothelial cells could play a crucial role in neurovascular coupling during synaptic activity. The neurotransmitter glutamate increases cerebral blood flow  by activating postsynaptic neurons and presynaptic glial cells within the neurovascular unit. Glutamate does so by causing an increase in intracellular Ca2+ concentration ([Ca2+]i) in the target cells, which activates the Ca2+/Calmodulin ‐dependent nitric oxide (NO) synthase to release NO. It is unclear whether brain endothelial cells also sense glutamate through an elevation in [Ca2+]i and NO production. The current study assessed whether and how glutamate drives Ca2+‐dependent NO release in bEND5 cells, an established model of brain endothelial cells. We found that glutamate induced a dose‐dependent oscillatory increase in [Ca2+]i, which was maximally activated at 200  μM and inhibited by α‐methyl‐4‐carboxyphenylglycine, a selective blocker of Group 1 metabotropic glutamate receptors. Glutamate‐induced intracellular Ca2+ oscillations were triggered by rhythmic endogenous Ca2+ mobilization and maintained over time by extracellular Ca2+ entry. Pharmacological manipulation revealed that glutamate ‐induced endogenous Ca2+ release was mediated by InsP3‐sensitive receptors and n...
Source: Journal of Cellular Physiology - Category: Cytology Authors: Tags: ORIGINAL RESEARCH ARTICLE Source Type: research