Signaling from Blood Vessels to CNS Axons through Nitric Oxide

• DOI: 10.1523/jneurosci.1528-06.2006
• Publication Date: 2006-07-19T17:29:52Z
• Authors: Giti Garthwaite; Katalin Bartus; Denise Malcolm; David Goodwin; Martha Kollb-Siel...; Chaminda Dooldeniya; John Garthwaite
• Keywords: 0301 basic medicine; CURRENT I-H; Nitric Oxide Synthase Type III; Cyclic Nucleotide-Gated Cation Channels; Mice, Inbred Strains; In Vitro Techniques; Bradykinin; Nitric Oxide; optic nerve; Ion Channels; HCN channels; Mice; 03 medical and health sciences; SYNAPTIC PLASTICITY; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Animals; Cyclic GMP; Mice, Knockout; HYPERPOLARIZATION-ACTIVATED CURRENT; nitric oxide synthase; MICE DEFICIENT; RAT OPTIC-NERVE; Microcirculation; Brain; Endothelial Cells; Optic Nerve; cGMP; Electrophysiology; Isoenzymes; endothelial cell; Blood Vessels; LONG-TERM POTENTIATION; SOLUBLE GUANYLYL CYCLASE; bradykinin; Nitric Oxide Synthase; MYELINATED AXONS; WHITE-MATTER; NEUROTROPHIC FACTOR

Brain function is usually perceived as being performed by neurons with the support of glial cells, network blood vessels situated nearby serving simply to provide nutrient and dispose metabolic waste. Revising this view, we find from experiments on a rodent central white matter tract (the optic nerve) in vitro that microvascular endothelial cells signal persistently axons using nitric oxide (NO) derived NO synthase (eNOS). The endogenous acts stimulate guanylyl cyclase-coupled receptors axons, leading raised cGMP level which then causes membrane depolarization, apparently directly engaging hyperpolarization-activated cyclic nucleotide-gated ion channels. tonic depolarization associated NO-dependent generation was absent nerves mice lacking eNOS, although such responded exogenous NO, depolarization. In addition activity, exposure bradykinin, classical stimulator eNOS elicited reversible NO- cGMP-dependent through activation bradykinin B 2 receptors, physically complexed. No contribution other isoforms either action or continuous ambient could be detected. results suggest participate processing brain can do so generating both phasic signals.