Gas Diffusion in the CNS

Abstract

Gases have been long known to have essential physiological functions in the CNS such as respiration or regulation of vascular tone. Since gases have been classically considered to freely diffuse, research in gas biology has so far focused on mechanisms of gas synthesis and gas reactivity, rather than gas diffusion and transport. However, the discovery of gas pores during the last two decades and the characterization of diverse diffusion patterns through different membranes has raised the possibility that modulation of gas diffusion is also a physiologically relevant parameter. Here we review the means of gas movement into and within the brain through "free" diffusion and gas pores, notably aquaporins, discussing the role that gas diffusion may play in the modulation of gas function. We highlight how diffusion is relevant to neuronal signaling, volume transmission, and cerebrovascular control in the case of NO, one of the most extensively studied gases. We point out how facilitated transport can be especially relevant for gases with low permeability in lipid membranes like NH and discuss the possible implications of NH -permeable channels in physiology and hyperammonemic encephalopathy. We identify novel research questions about how modulation of gas diffusion could intervene in CNS pathologies. This emerging area of research can provide novel and interesting insights in the field of gas biology.

Extrasynaptic Neurotransmission Mediated by Exocytosis and Diffusive Release of Transmitter Substances

“…Increases in the intracellular calcium levels in the presence of the enzyme nitric-oxide-synthase (NOS), a calcium-calmodulin enzyme, produces NO from its precursor L-arginine (see Garthwaite et al, 1988 ; Bredt and Snyder, 1990 ; Garthwaite, 2008 , 2016 ). The mechanism of NO inactivation remains unclear, although cytochrome P450 oxidoreductase and astrocytes seem to contribute (Hall et al, 2009 ; Rodriguez-Grande and Konsman, 2018 ).…”

Aquaporins through the brain in health and disease: From water to gas movements

“…Recently, this central pore has also been shown to be permeable to cations and gases such as O 2 , CO 2 , NO, and NH 3 for AQP1 and AQP4. Interestingly, while AQP3, AQP8, and AQP9 seem to be only permeable to NH 3 , AQP5 can let both CO 2 and NH 3 pass through (Herrera, Hong, & Garvin, ; Itel et al, ; Musa‐Aziz, Chen, Pelletier, & Boron, ; Rodriguez‐Grande & Konsman, ; Yu, Yool, Schulten, & Tajkhorshid, ). This unique property is opening a new range of physiological functions for the AQPs such as the regulation of CO 2 permeability.…”

“…The AQP assembly into homotetramer and larger structure like orthogonal array of particles (see b) result in the formation of pores, shown to be permeable to cations and gases (green arrows). Gases can also diffuse through the Aquapore (for details see review in Rodriguez‐Grande & Konsman, ). (b) Schematic drawing of the orthogonal arrays of particles (OAP) formed in part by the association of the AQP4's two isoforms: long‐ (AQP4‐m1) and short‐splice variants (AQP4‐m23).…”

“…However, this “In Focus” section of the Journal of Neuroscience Research highlights additional new functions for AQPs in the CNS. While the research article from Simon, Murchison, & Iliff () presents exciting new developments on the formation of the complex of channels, transporters, and other proteins associated with AQP4 in astrocyte endfeet, the work by Hirt et al () points out the key role of AQP9 in astrogliosis after brain injury, and the review by Rodriguez‐Grande & Konsman () focuses on the importance of AQPs in gas diffusion for the CNS.…”

“…This opens the exciting possibility of a novel gas level regulation process across cellular membranes, a relevant parameter for brain physiology. Rodriguez‐Grande & Konsman () review the importance of gas movement into and within the brain via gas pores and, in particular, AQPs. The modulation of gas diffusion, in particular NO, is central in neuronal signaling and cerebrovascular control.…”