title: Extracellular ionic and volume changes: the role in glia-neuron interaction.
abstract: Activity-related changes in extracellular K+ concentration ([K+]e), pH (pHe) and extracellular volume were studied by means of ion-selective microelectrodes in the adult rat spinal cord in vivo and in neonatal rat spinal cords isolated from pups 3-14 days of age (P3-P14). Concomitantly with the ionic changes, the extracellular space (ECS) volume fraction (alpha), ECS tortuosity (lambda) and non-specific uptake (kappa'), three parameters affecting the diffusion of substances in nervous tissue, were studied in the rat spinal cord gray matter. In adult rats, repetitive electrical nerve stimulation (10-100 Hz) elicited increases in [K+]e of about 2.0-3.5 mM, followed by a post-stimulation K(+)-undershoot and triphasic alkaline-acid-alkaline changes in pHe with a dominating acid shift. The ECS volume in the adult rat occupies about 20% of the tissue, alpha = 0.20 +/- 0.003, lambda = 1.62 +/- 0.02 and kappa' = 4.6 +/- 0.4 x 10(-3) s-1 (n = 39). In contrast, in pups at P3-P6, the [K+]e increased by as much as 6.5 mM at a stimulation frequency of 10 Hz, i.e. K+ ceiling level was elevated, and there was a dominating alkaline shift. An increase in [K+]e as large as 1.3-2.5 mM accompanied by an alkaline shift was evoked by a single electrical stimulus. The K+ ceiling level and alkaline shifts decreased with age, while an acid shift, which was preceded by a small initial alkaline shift, appeared in the second postnatal week. In pups at P1-P2, the spinal cord was X-irradiated to block gliogenesis. The typical decrease in [K+]e ceiling level and the development of the acid shift in pHe at P10-P14 were blocked by X-irradiation. Concomitantly, continuous development of glial fibrillary acidic protein positive reaction was disrupted and densely stained astrocytes in gray matter at P10-P14 revealed astrogliosis. The alkaline, but not the acid, shift was blocked by Mg2+ and picrotoxin (10(-6) M). Acetazolamide enhanced the alkaline but blocked the acid shift. Furthermore, the acid shift was blocked, and the alkaline shift enhanced, by Ba2+, amiloride and SITS. Application of glutamate or gamma-aminobutyric acid evoked an alkaline shift in the pHe baseline at P3-P14 as well as after X-irradiation. The results suggest that the activity-related acid shifts in pHe are related to membrane transport processes in mature glia, while the alkaline shifts have a postsynaptic origin and are due to activation of ligand-gated ion channels.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Laboratory of Cellular Neurophysiology, Academy of Sciences of the Czech Republic, Prague.
authors.forename: E
authors.initials: E
authors.lastname: Syková
authors.forename: A
authors.initials: A
authors.lastname: Chvátal
mesh_terms: D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000086:Acetazolamide / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002450:Cell Communication; D004558:Electric Stimulation; D005110:Extracellular Space / Q000502:physiology; D005260:Female; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006706:Homeostasis; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D015636:Magnesium Chloride / Q000494:pharmacology; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000254:growth & development / Q000502:physiology* / Q000528:radiation effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D005971:Glutamates; D000644:Quaternary Ammonium Compounds; D015636:Magnesium Chloride; D001464:Barium; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000584:Amiloride; C027917:tetramethylammonium; D000086:Acetazolamide; D011188:Potassium