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. The depolarization 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 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 normal propagation of an action potential.

Potassium regulatory mechanisms

mechanisms behind potassium buffering can be broadly categorized as either K+ uptake or K+ spatial buffering.

Evidence of potassium spatial buffering

First support of potassium spatial buffering was supported by classic work by Orkand et al, where amphibians, when the optic nevers were stimulated, lead to slow deplolarization and repolarization in glial cells surrounding the nonmyelinated axons.

Potassium siphoning

Potassium spatial buffering that occurs in retinas, where the muller cell is the principal glial cell type, is called potassium siphoning.

Kir Channel

K+ spatial buffering is the process by which glial cells dissipate local potassium gradient by transferring potassium ions from high to low concentration. The inward potassium fluxes are mainly mediated by rectifying K+(Kir)channels.

Diseases

In patients with Tuberous Sclerosis Complex (TSC), abnormalities occur in astrocyte, which leads to pathogenesis of neurological dysfunction in this disease. TSC is a multisystem genetic disease with mutation in either TSC1 or TSC2 gene. It results in disabling neurological symptoms such as mental retardation, autism, and seizures. Glial cells have important physiological roles of regulating neuronal excitability and preventing epilepsy. Astrocytes maintain homeostasis of excitatory substances, such as extracellular potassium, by immediate uptake through specific potassium channels and sodium potassium pumps. It is also regulated by potassium spatial buffering via astrocyte networks where astrocytes are coupled through gap junctions. Mutations in TSC1 or TSC2 gene often results in decreased expression of the astrocytic connexin protein, Cx43. With impairment in gap junction coupling between astrocytes, myriad of abnormalities in potassium buffering occurs which results in increased extracellular potassium concentration and may predispose to neuronal hyperexcitability and seizures.

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.