Calcium Compartments in Brain

• Published in: Journal of cerebral blood flow and metabolism Vol. 22; no. 4; pp. 479 - 489
• Main Authors: Newman, George C., Hospod, Frank E., Patlak, Clifford S., Trowbridge, Sean D., Wilke, Richard J., Fuhrmann, Mark, Jones, Keith W.
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-04-2002; Lippincott Williams & Wilkins; Sage Publications Ltd
• Subjects: Animals; BASIC BIOLOGICAL SCIENCES; Biochemistry and metabolism; Biological and medical sciences; BRAIN; BUFFERS; CALCIUM; Calcium - metabolism; Calcium Radioisotopes - metabolism; Central nervous system; COMPARTMENTS; DATA; EMISSION; EQUILIBRIUM; Fundamental and applied biological sciences. Psychology; GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE; Hippocampus - cytology; Hippocampus - metabolism; HISTOLOGY; In Vitro Techniques; ISOTHERMS; KINETICS; Male; Mathematics; MEMBRANES; Models, Neurological; national synchrotron light source; PHARMACOLOGY; PHYSIOLOGY; PLASMA; POTENTIALS; RANGE; Rats; Rats, Sprague-Dawley; SIZE; Vertebrates: nervous system and sense organs; Calcium; Brain; Kinetics; Radionuclide study; Cell compartment; Rat; Rodentia; Central nervous system; Cell biology; Metabolism; Pathology; Kinetic model; Vertebrata; Compartmental model; Mammalia; Calcium ion; Animal; Physiology; Ion exchange; Hippocampus; Brain (vertebrata)
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1097/00004647-200204000-00012

Excellent progress has been made toward understanding the physiology and pharmacology of specific calcium-related cellular processes of the brain, but few studies have provided an integrated view of brain calcium kinetics. To further the knowledge of the size and binding properties of brain calcium compartments, the authors have conducted a series of experiments in hippocampal brain slices exposed to high and low extracellular calcium. Slices were incubated in buffers containing 0.001 to 4.5 mmol/L calcium for up to 75 minutes. Slice calcium content was analyzed by three methods: exchange equilibrium with 45Ca, synchrotron-radiation–induced x-ray emission, and inductively coupled plasma. Data were analyzed using a model based on a Langmuir isotherm for two independent sites, with additional extracellular and bound compartments. In parallel experiments, altered low calcium had no effect on slice histology and only mild effects on slice adenylates. When combined with prior 45Ca and fluorescent probe binding experiments, these results suggest that there are at least five kinetically distinct calcium compartments: (1) free extracellular (∼10%); (2) loosely associated extracellular plasma membrane (∼55%); (3) intracellular compartment with moderate avidity (∼17%); (4) tightly bound, nonexchangeable intracellular compartment (∼15%); and (5) free cytoplasmic (<0.01%). If only the third compartment is considered a potential calcium buffer, then the buffering ratio is calculated to be ∼2,700:1, but if the second compartment is also included, then the buffering ratio would be ∼13,000:1. This may explain the wide range of estimates observed by fluorescent probe studies.