Control of Extracellular Potassium Levels by Retinal Glial Cell K ⁺ Siphoning

Abstract

Efflux of K + from dissociated salamander Müller cells was measured with ion-selective microelectrodes. When the distal end of an isolated cell was exposed to high concentrations of extracellular K + , efflux occurred primarily from the endfoot, a cell process previously shown to contain most of the K + conductance of the cell membrane. Computer simulations of K + dynamics in the retina indicate that shunting ions through the Müller cell endfoot process is more effective in clearing local increases in extracellular K + from the retina than is diffusion through extracellular space. We have suggested that the retinal Müller cell, a specialized astrocyte that spans nearly the entire width of the retina, buffers changes in retinal [K + ] o (4,5). We have shown that amphibian Müller cells are almost exclusively permeable to K + (6) and that 94 percent of the total K + conductance in these cells occurs in the Müller cell endfoot, a process lying adjacent to the vitreous humor (4). This highly asymmetric K + conductance distribution may make the process of K + spatial buffering more powerful than has been recognized. For example, nearly all of the K + current entering Müller cells from regions of increased [K + ] o within the retina may leave the Müller cell endfoot process at the vitreo-retinal border. Thus, the vitreous would function as a large potassium sink.We now present experimental evidence of extracellular K + buffering by Müller cells which utilizes this asymmetric conductance distribution. Dissociated Müller cells from the salamander Ambystoma tigrinum were prepared and maintained as described (4). The distal end of the Müller cell surface was exposed to increased [K + ] o by pressure-ejecting an 85 mM KCl-Ringer solution from an extracellular pipette (approximately 3 µm in tip diameter). Perfusate near this ejection pipette was drawn into a suction pipette (30 µm in diameter) to

Seizures and disturbed brain potassium dynamics in the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts

“…Both these proteins are necessary for [K + ] o regulation and have been linked to seizures. K ir 4.1 is crucial for K + spatial buffering49, 50, 51 and for efflux of K + from astrocytes following active transport 48. Astrocyte‐specific K ir 4.1 conditional knockout results in reduced astrocyte K + uptake, disturbed clearance of [K + ] o , white matter vacuolization, ataxia, and stress‐induced seizures,15, 16 thereby resembling the MLC phenotype.…”

Role of enteric glial cells in inflammatory bowel disease

“…Furthermore, passive currents have been observed among gap junction-coupled EGCs in isolated ganglia (Hanani et al, 2000). All of these features suggest that EGCs buffer excess extracellular K ϩ ions released during neuronal activity via inward-acting potassium channels, and intracellular K ϩ is then re- distributed via the glial syncytium into areas of low extracellular K ϩ concentrations (Newman et al, 1984;Newman, 1986Newman, , 1993.…”

“…Due to the potential excitotoxicity effects that this may have on enteric neurons, extracellular ion concentrations need to be strictly controlled. CNS astrocytes have the capacity to buffer extracellular K ϩ ions (Orkand et al, 1966;Newman et al, 1984;Newman, 1986Newman, , 1993Verkhratsky and Steinhä user, 2000). Interestingly, EGCs share these phenotypic and functional properties with astrocytes.…”

Astrocytes in Alzheimer's Disease

“…29 Extracellular K ϩ homeostasis is mainly carried out by astrocytes through local K ϩ uptake (via inward rectifier K ϩ channels) and spatial K ϩ buffering. 29,30 The spatial K ϩ buffering is achieved through redistribution of K ϩ within glial syncytia or even within single polarized glial cells from the areas with elevated [K ϩ ] o to the regions with low [K ϩ ] o . This K ϩ uptake and spatial buffering is coupled with astroglial water transport.…”