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Ion Regulation in the Brain: Implications for Pathophysiology

Departments of Cell Biology and Neurobiology Duke University Medical Center Durham, North Carolina;Box 3709, Duke University Medical Center, Durham, NC 27710; g.somjen{at}cellbio.duke.edu

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., pH_o 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).

Key Words: Ion regulation • Cerebral interstitial fluid • Cerebrospinal fluid • Blood-brain barrier • Seizures • Cerebral ischemia

The Neuroscientist, Vol. 8, No. 3, 254-267 (2002)
DOI: 10.1177/1073858402008003011


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