Potassium spatial buffering
Potassium spatial buffering is a mechanism for the regulation of extracellular potassium concentration by astrocytes. Other mechanisms for astrocytic potassium clearance are carrier-operated or channel-operated potassium chloride uptake.[1] The repolarization of neurons tends to raise potassium concentration in the extracellular fluid. If a significant rise occurs, it will interfere with neuronal signaling by depolarizing neurons. Astrocytes have large numbers of potassium ion channels facilitating the removal of potassium ions from the extracellular fluid. They are taken up at one region of the astrocyte and then distributed throughout the cytoplasm of the cell, and further to its neighbors via gap junctions. This keeps extracellular potassium at levels that prevent interference with the normal propagation of an action potential.
Potassium spatial buffering
Glial cells, once believed to have a passive role in CNS, are active regulators of numerous functions in the brain, including clearance of the neurotransmitter from the synapses, guidance during neuronal migration, control of neuronal synaptic transmission, and maintaining an ideal ionic environment for active communications between neurons in central nervous system.[2]
Neurons are surrounded by extracellular fluid rich in sodium ions and poor in potassium ions. The concentrations of these ions are reversed inside the cells. Due to the difference in concentration, there is a chemical gradient across the cell membrane, which leads to sodium influx and potassium efflux. When the action potential takes place, a considerable change in extracellular potassium concentration occurs due to the limited volume of the CNS extracellular space. The change in potassium concentration in the extracellular space impacts a variety of neuronal processes, such as maintenance of membrane potential, activation and inactivation of voltage gated channels, synaptic transmission, and electrogenic transport of neurotransmitters. Change of extracellular potassium concentration of from 3mM can affect neural activity. Therefore, there are diverse cellular mechanisms for tight control of potassium ions, the most widely accepted mechanism being K+ spatial buffering mechanism. Orkand and his colleagues who first theorized spatial buffering stated “if a Glial cell becomes depolarized by K+ that has accumulated in the clefts, the resulting current carries K+ inward in the high [K+] region and out again, through electrically coupled Glial cells in low [K+] regions” In the model presented by Orkand and his colleagues, glial cells intake and traverse potassium ions from region of high concentrations to region of low concentration maintaining potassium concentration to be low in extracellular space. Glial cells are well suited for transportation of potassium ions since it has unusually high permeability to potassium ions and traverse long distance by its elongated shape or by being coupled to one another.[3][4]
Potassium regulatory mechanisms
Potassium buffering can be broadly categorized into two categories: Potassium uptake and Potassium spatial buffering. For potassium uptake, excess potassium ions are temporarily taken into glial cells through transporters, or potassium channels. In order to preserve electroneutrality, potassium influxes into glial cells are accompanied by influx of chlorine or efflux of sodium. It is expected that when potassium accumulates within glial cells, water influx and swelling occurs. For potassium spatial buffering, functionally coupled glial cells with high potassium permeability transfer potassium ions from regions of elevated potassium concentration to regions of lower potassium concentration. The potassium current is driven by the difference in glial syncytium membrane potential and local potassium equilibrium potential. When one region of potassium concentration increases, there is a net driving force causing potassium to flow into the glial cells. The entry of potassium causes a local depolarization that propagates electrotonically through the glial cell network which causes net driving force of potassium out of the glial cells. This process causes dispersion of local potassium with little net gain of potassium ions within the glial cells, which in turn prevents swelling. Glial cell depolarization caused by neuronal activity releases potassium onto bloodstream, which was once widely hypothesized to be cause of vessel relaxation, was found to have little effect on neurovascular coupling.[5] Despite the efficiency of potassium spatial buffering mechanisms, in certain regions of CNS, potassium buffering seems more dependent on active uptake mechanisms rather than spatial buffering. Therefore, the exact role of glial potassium spatial buffering in the various regions of our brain still remains uncertain.[6]
Kir channel
The high permeability of glial cell membranes to potassium ions is a result of expression of high densities of potassium-selective channels with high open-probability at
Kir channels are categorized into seven major subfamilies, Kir1 to Kir7, with a variety of gating mechanisms. Kir3 and Kir6 are primarily activated by intracellular
Panglial syncytium
The panglial syncytium is a large network of interconnected glial cells, which are extensively linked by gap junctions. The panglial syncytium spreads through central nervous system where it provides metabolic and osmotic support, as well as ionic regulation of myelinated axons in white matter tracts. The three types of macroglial cells within network of panglial syncytium are
Potassium siphoning
Potassium spatial buffering that occurs in the retina is called potassium siphoning, where the
History
Existence of potassium siphoning was first reported in 1966 study by Orkand et al. In the study, optic nerve of Necturus was dissected to document the long-distance movement of potassium after the nerve stimulation. Following the low frequency stimulation of .5 Hz at the retinal end of the dissected optic nerve, depolarization 1-2mV was measured at astrocytes at the opposite end of the nerve bundle, which was up to several millimeters from the electrode. With higher frequency stimulation, higher plateau of depolarization was observed. Therefore, they hypothesized that the potassium released to extracellular compartment during axonal activity entered and depolarized nearby astrocytes, where it was transported away by unfamiliar mechanism, which caused depolarization on astrocytes distant from site of stimulation. The proposed model was actually inappropriate since at the time neither gap junctions nor syncytium among glial cells were known, and optic nerve of Necturus are unmyelinated, which means that potassium efflux occurred directly into the periaxonal extracellular space, where potassium ions in extracellular space would be directly absorbed into the abundant astrocytes around axons.[14]
Diseases
In patients with
Demyelinating Diseases of the central nervous system, such as Neuromyelitis Optica, often leads to molecular components of the panglial syncytium being compromised, which leads to blocking of potassium spatial buffering. Without mechanism of potassium buffering, potassium induced osmotic swelling of myelin occurs where myelins are destroyed and axonal salutatory conduction ceases.[17]
References
- ^ Walz W (2000): Role of astrocytes in the clearance of excess extracellular potassium. Neurochemistry International
- ^ Kozoriz, M. G., D. C. Bates, et al. (2006). "Passing potassium with and without gap junctions." Journal of Neuroscience 26(31): 8023-8024.
- ^ Chen, K. C. and C. Nicholson (2000). "Spatial buffering of potassium ions in brain extracellular space." Biophysical Journal 78(6): 2776-2797.
- ^ Xiong, Z. Q. and F. L. Stringer (2000). "Sodium pump activity, not glial spatial buffering, clears potassium after epileptiform activity induced in the dentate gyrus." Journal of Neurophysiology 83(3): 1443-1451.
- ^ Metea, M. R., P. Kofuji, et al. (2007). "Neurovascular coupling is not mediated by potassium siphoning from glial cells." Journal of Neuroscience 27(10): 2468-2471.
- ^ Kofuji, P. and E. A. Newman (2004). "Potassium buffering in the central nervous system." Neuroscience 129(4): 1045-1056.
- ^ Kofuji, P. and N. C. Connors (2003). "Molecular substrates of potassium spatial buffering in glial cells." Molecular Neurobiology 28(2): 195-208.
- ^ Solessio, E., K. Rapp, et al. (2001). "Spermine mediates inward rectification in potassium channels of turtle retinal Muller cells." Journal of Neurophysiology 85(4): 1357-1367.
- ^ Rash, J. E. (2010). "Molecular Disruptions of the Panglial Syncytium Block Potassium Siphoning and Axonal Saltatory Conduction: Pertinence to Neuromyelitis Optica and Other Demyelinating Diseases of the Central Nervous System." Neuroscience 168(4): 982-1008.
- ^ Brew, H. and D. Attwell (1985). "Is the Potassium Channel Distribution in Glial-Cells Optimal for Spatial Buffering of Potassium." Biophysical Journal 48(5): 843-847.
- ^ Karwoski, C. J., H. K. Lu, et al. (1989). "Spatial Buffering of Light-Evoked Potassium Increases by Retinal Muller (Glial) Cells." Science 244(4904): 578-580.
- ^ Newman, E. A., D. A. Frambach, et al. (1984). "Control of Extracellular Potassium Levels by Retinal Glial-Cell K+ Siphoning." Science 225(4667): 1174-1175.
- ^ Winter, M., W. Eberhardt, et al. (2000). "Failure of potassium siphoning by Muller cells: A new hypothesis of perfluorocarbon liquid-induced retinopathy." Investigative Ophthalmology & Visual Science 41(1): 256-261.
- ^ Kofuji, P. and E. A. Newman (2004). "Potassium buffering in the central nervous system." Neuroscience 129(4): 1045-1056.
- ^ Xu, L., L. H. Zeng, et al. (2009). "Impaired astrocytic gap junction coupling and potassium buffering in a mouse model of tuberous sclerosis complex." Neurobiology of Disease 34(2): 291-299.
- ^ Wallraff, A., R. Kohling, et al. (2006). "The impact of astrocytic gap junctional coupling on potassium buffering in the hippocampus." Journal of Neuroscience 26(20): 5438-5447.
- ^ Rash, J. E. (2010). "Molecular Disruptions of the Panglial Syncytium Block Potassium Siphoning and Axonal Saltatory Conduction: Pertinence to Neuromyelitis Optica and Other Demyelinating Diseases of the Central Nervous System." Neuroscience 168(4): 982-1008.