Potassium homeostasis and glial energy metabolism

Abstract

Since capillaries appear not to contribute significantly to rapid removal of K+ from brain tissue, the K+ released into extracellular clefts by neurons at the onset of electrical activity is presumably removed either by redistribution in the clefts or by uptake into cells. What appear to be the three major processes require no energy from the glial cells. These are diffusion through the extracellular clefts, spatial buffering by glial cells, and net uptake of K+ into glial cells through glial K+ channels associated with uptake of Cl−through an independent Cl‐ conductance. There is a relatively slow uptake by the Na+/K+‐ATPase, which directly consumes ATP. In addition, some glial cells take up K+ on the Na+/K+/2Cl‐ cotransporter, which leads indirectly to energy consumption when the Na+ is subsequently pumped out. Currently available data suggest that the glial energy metabolism devoted to K+ homeostasis is less than a tenth of the total tissue energy metabolism, even under conditions of pathologically high extracellular [K+]. Hence, in situ, it is possible that glial cells could function with much less ATP than neurons do. All the various routes of muffling of changes in extracellular [K+] can be modulated, directly or indirectly, by transmitters liberated by neurons. A consequence of this could be regulation of the entry of Na+ into glial cells such that the Na+/K+‐ATPase is activated. The degree of activation might be adjusted so that the resulting activation of the glial glycolytic pathway is appropriate to the provision of the quantity of metabolic substrates required by the neurons. GLIA 21:46–55, 1997. © 1997 Wiley‐Liss, Inc.

Detecting Activity in Olfactory Bulb Glomeruli with Astrocyte Recording

“…Removal of K ϩ from the extracellular space (Amédée et al, 1997;Kofuji and Newman, 2004) and clearance of glutamate from the synaptic cleft (Danbolt, 2001) are two well known functions of astrocytes in the brain. Both mechanisms produce currents in glial cells that are caused by and reflect neuronal activity, as illustrated by our recordings from olfactory bulb astrocytes.…”

“…Astrocytes are thought to use IRK channels to remove K ϩ from regions with high extracellular K ϩ and release it to regions with low K ϩ , a mechanism known as spatial buffering or siphoning of K ϩ (Karwoski et al, 1989;Amédée et al, 1997;Kofuji and Newman, 2004). In the retina, Kir4.1 channels are the main channels involved in the regulation of external K ϩ (Kofuji et al, 2000).…”

“…At this concentration, Ba 2ϩ effectively blocks inward rectifier K ϩ channels (IRKs) that are highly expressed in glial cells (Newman, 1993). IRKs are thought to be involved in the spatial buffering of K ϩ released in the extracellular space during neuronal activity (Karwoski et al, 1989;Newman, 1993;Amédée et al, 1997;Kofuji and Newman, 2004). Because K ϩ accumulates in the glomerular layer after OSN stimulation (Jahr and Nicoll, 1981;Khayari et al, 1988;Friedrich and Korsching, 1998), the Ba 2ϩ -sensitive component is consistent with IRK-dependant current in response to extracellular K ϩ accumulation.…”

“…In vitro, extracellular potassium increases within glomeruli after afferent stimulation (Jahr and Nicoll, 1981;Khayari et al, 1988;Friedrich and Korsching, 1998). Glial barriers that remove extracellular potassium (Amédée et al, 1997;Kofuji and Newman, 2004) may prevent the spread of activity (Goriely et al, 2002).…”

Aquaporin-4 Water Channel Protein in the Rat Retina and Optic Nerve: Polarized Expression in Müller Cells and Fibrous Astrocytes

“…Because the C NS possesses a narrow extracellular space, the excess extracellular K ϩ cannot always be efficiently cleared by simple diff usion but will have to be buffered by uptake into a cellular compartment (Gardner-Medwin, 1993a,b). Glial cells figure prominently in this regard and have been shown to remove excess K ϩ from the extracellular cleft by active and passive uptake as well as by K ϩ spatial currents (for review, see Walz, 1989;Newman, 1995;Amédée et al, 1997). The latter two mechanisms for K ϩ removal tend to cause a reduction in extracellular osmolarity, presenting an osmotic challenge to glial cells as well as to neurons (Dietzel et al, 1989).…”