Model of potassium dynamics in the central nervous system

Abstract

A one-dimensional numerical model of potassium dynamics in the central nervous system is developed. The model incorporates the following physiological processes in computing spatial and temporal changes in extracellular K+ concentration, [K+],: 1) the release of K + from K+ sources into extracellular space, 2) diffusion of Kf through extracellular space, 3) active uptake of K + into cells and blood vessels, 4) passive uptake of K+ into a cellular distribution space, and 5) the transfer of K + by K + spatial buffer current flow in glial cells. The following tissue parameters can be specified along the single spatial dimension of the model: 1) the volume fraction and tortuosity of extracellular and glial cell spaces, 2) the volume fraction of the cellular distribution space, 3) rate constants of active uptake and passive uptake processes, and 4) glial cell membrane conductance. The model computes variations in [K+], and current flow through glial cells for three tissue geometries: 1) planar geometry (the retina and the surface of the brain), 2) cylindrical geometry (tissue surrounding a blood vessel), and 3) spherical geometry (tissue surrounding a point source of Kf). For simple sources of K f , the performance of the model matches that predicted from analytical equations. Simulations of previous ion dynamics experiments indicate that the model can accurately predict ion diffusion and K+ current flow in the brain. Simulations of electroretinogram generation and K + siphoning onto blood vessels suggest that unanticipated K' dynamics mechanisms may be operating in the central nervous system.

Potassium channel Kir4.1 macromolecular complex in retinal glial cells

“…Modeling studies (Odette and Newman, 1988) suggest that the enrichment of K 1 channels at the endfeet of M€ uller cells enhance K 1 buffering. Our studies show a redistribution of K 1 conductances in the mdx 3Cv mouse which could potentially alter K 1 fluxes in retina.…”

“…A unique property of Kir4.1 within these cells is its subcellular localization, being highly concentrated in M€ uller cell endfeet and in perivascular processes (Nagelhus et al, 1999;Kofuji et al, 2000). This localization pattern is thought to facilitate the potassium siphoning mechanism by enrichment of Kir4.1 in cellular regions where K 1 can be released from M€ uller cells without altering the stability of neuronal physiology (Odette and Newman, 1988;Newman and Reichenbach, 1996).…”

The roadmap for estimation of cell-type-specific neuronal activity from non-invasive measurements

“…K ir channels are also present in the endothelial cells [96] and can underlie EC-mediated propagation of signalling along the vascular wall [97]. Glial role in K þ transport from the extracellular to perivascular space (known as 'K þ siphoning') has also been proposed but remains controversial [98][99][100]. Although further studies are required to document the role of K ir channels in local and conducted vasodilation in vivo, one or more of these K þ -mediated mechanisms may account for the residual dilation response insensitive to the blockers of molecular signalling.…”

Release of chemical transmitters from cell bodies and dendrites of nerve cells

“…Therefore, activity of nerve cells, irrespective of their transmitters, depolarizes glial cells (by potassium liberation), which in turn generates a local increase in blood flow just where it is most needed. A function for glial cells that had been suggested many years ago [40] has now been shown to be of crucial importance.…”