Chloride/anion channels in glial cell membranes

Abstract

At least seven different chloride/anion currents have now been identified in astrocytes, oligodendrocytes/Schwann cells, and microglia. Only for two of these currents is the corresponding gene known. One of these genes is not encoding for a chloride channel, but for a class of mitochondria-like pores also found in cell membranes. Astrocytes and oligodendrocytes differ in their resting properties: astrocytes accumulate chloride but do not have a significant permeability. Oligodendrocytes have a close to passive distribution and a significant permeability. Under certain circumstances, astrocytes can express a resting chloride conductance. Reactive and neoplastic astrocytes as well as astrocytes with an altered shape exhibit a resting conductance. The function of these channels certainly involves volume regulation. Other possible functions are potassium homeostasis, migration, proliferation (in microglia), and involvement in spreading depression waves. Of greatest interest are two phenomena discovered in situ: The ClC-2 channel is only found in astrocytic endfeet near blood capillaries adjacent to neuronal GABA A receptors. In the supraoptic nucleus of the hypothalamus, there is an osmosensitive astrocytic taurine release. This released taurine interacts with glycine receptors in neighboring neurons, causing inhibition. It is assumed that with the future availability of more in situ, rather than in vitro, studies, an increased number of such complex interactions between glial cells, neurons, and blood vessels will be discovered.

Leukoencephalopathy upon Disruption of the Chloride Channel ClC-2

“…Thus, it is plausible that ClC-2 mediates Cl Ϫ efflux in astrocytic endfeet, in particular because the parallel efflux of K ϩ (via channels containing Kir4.1) will increase the open probability of ClC-2 by hyperpolarizing the membrane ). An influx of Cl Ϫ via ClC-2 is more easily imaginable in oligodendrocytes, in which the electrochemical potential for Cl Ϫ is probably at, or slightly above, equilibrium (Walz, 2002). We propose that ClC-2 might serve both as an influx and efflux pathway for Cl Ϫ , influenced by the activitydependent electrochemical gradients present at specific subcellular sites.…”

“…The direction of passive Cl Ϫ transport depends on the electrochemical potential for Cl Ϫ . Several studies indicate that it is above equilibrium in astrocytes (Walz, 2002). Thus, it is plausible that ClC-2 mediates Cl Ϫ efflux in astrocytic endfeet, in particular because the parallel efflux of K ϩ (via channels containing Kir4.1) will increase the open probability of ClC-2 by hyperpolarizing the membrane ).…”

Chloride Accumulation Drives Volume Dynamics Underlying Cell Proliferation and Migration

“…This is likely due to the fact that in most mature neurons, intracellular [Cl Ϫ ] is quite low (ϳ10 mM) and primarily serves to stabilize the resting membrane potential on opening of GABA-gated channels (Kaila 1994). Yet mature astrocytes accumulate chloride to levels approximately four times what would be determined by passive distribution (Walz 2002). Further all proliferating cells in the brain, including the immature neurons of development and the neural stem cells (NSCs) in the adult actively accumulate chloride (Achilles et al 2007;Kakazu et al 1999;Kuner and Augustine 2000) such that these cells exhibit a characteristic depolarizing response to ␥-aminobutyric acid (GABA)-mediated chloride channel opening.…”

Optically Recorded Response of the Superficial Dorsal Horn: Dissociation From Neuronal Activity, Sensitivity to Formalin-Evoked Skin Nociceptor Activation

“…Glial activation involves changes in astrocyte shape and volume and altered communication between neighboring astrocytes via gap junctions (Meme et al 2004;Olsen and Sontheimer 2004;Walz 2002). Astrocytes in the affected region of the dorsal horn exhibit increased expression of glial fibrillary acidic protein (GFAP) (Garrison et al 1991), decreased expression of glutamate transporters and K IR -type membrane potassium channels (Huang et al 2004;Kawahara et al 2002;MacFarlane and Sontheimer 1997;Olsen and Sontheimer 2004), increased Cl Ϫ conductance (Parkerson and Sontheimer 2004;Walz 2002), absence of the [Ca 2ϩ ] i transients normally evoked by afferent activity (Aguado et al 2002), and altered expression of genes regulating production and release of neuroactive cytokines, chemokines, growth factors, and NO (Meeuwsen et al 2003;Milligan et al 2001).…”