Ion regulation in the brain: implications for pathophysiology.
Ions in the brain are regulated independently from plasma levels by active transport across choroid plexus epithelium and cerebral capillary endothelium, assisted by astrocytes. In "resting" brain tissue, extracellular potassium ([K+]o) is lower and [H]o is higher (i.e., pHo is lower) than elsewhere in the body. This difference probably helps to maintain the stability of cerebral function because both high [K]o and low [H+]o enhance neuron excitability. Decrease in osmolarity enhances synaptic transmission and neuronal excitability whereas increased osmolarity has the opposite effect. Iso-osmotic low Na+ concentration also enhances voltage-dependent Ca2+ currents and synaptic transmission. Hypertonicity is the main cause of diabetic coma. In normally functioning brain tissue, the fluctuations in ion levels are limited, but intense neuronal excitation causes [K+]o to rise and [Na+]o, [Ca2+]o to fall. When excessive excitation, defective inhibition, energy failure, mechanical trauma, or blood-brain barrier defects drive ion levels beyond normal limits, positive feedback can develop as abnormal ion distributions influence neuron function, which in turn aggravates ion maldistribution. Computer simulation confirmed that elevation of [K+]o can lead to such a vicious circle and ignite seizures, spreading depression (SD), or hypoxic SD-like depolarization (anoxic depolarization).
Somjen
George G
GG
Department of Cell Biology and Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA. g.somjen@cellbio.duke.edu
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001693:Biological Transport, Active; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology*; D015220:Calcium Channels / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism; D002831:Choroid Plexus / Q000378:metabolism; D003198:Computer Simulation; D013181:Cortical Spreading Depression; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D009433:Neural Inhibition; D009994:Osmolar Concentration; D015221:Potassium Channels / Q000378:metabolism; D012640:Seizures / Q000378:metabolism* / Q000503:physiopathology*; D015222:Sodium Channels / Q000378:metabolism; D009435:Synaptic Transmission
D015220:Calcium Channels; D018118:Chloride Channels; D007473:Ion Channels; D015221:Potassium Channels; D015222:Sodium Channels; D008274:Magnesium