title: Astrocytes contribute to regulation of extracellular calcium and potassium in the rat cerebral cortex during spreading depression.
abstract: This study used spreading depression (SD), which is characterized by redistribution of ions, to examine the role of astrocytes in the regulation of extracellular potassium ([K+]o) and calcium ([Ca2+]o) levels. Recurrent spreading depression episodes were induced by application of 3 M potassium chloride to the cortex of adult anesthetized rats while monitoring the extracellular direct current (DC) potential shifts and changes in [K+]o or [Ca2+]o 6-7 mm away. The reversible glial toxins, fluorocitrate (FC) and fluoroacetate (FA), were injected locally into the cortex at doses that are selective for reducing glial function. The peak changes and area under the curve for [K+]o and [Ca2+]o, recovery rate for [K+]o, and interval between spreading depression episodes were measured before and at various times after administration of the toxins. Both fluorocitrate and fluroacetate slowed the recovery of the [K+]o and altered the recovery of the [Ca2+]o. Local injection of glutamate uptake inhibitors or barium had no effect on the peak changes in [K+]o or the rate of recovery of the [K+]o. The slowing of the recovery rate is consistent with the hypothesis that glial cells play a role in the return of [K+]o to baseline after spreading depression in the cortex in vivo. The change in movement of calcium after administration of FC suggests that astrocytes normally extrude calcium during spreading depression, resulting in rapid recovery of the levels of [Ca2+]o with an overshoot. These findings demonstrate that astrocytes contribute to the regulation of both potassium and calcium during and after a stress to the ionic homeostatic mechanisms.
authors.affiliation: Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Lian
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stringer
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002951:Citrates / Q000494:pharmacology; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology*; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002951:Citrates; C007744:fluorocitrate; D011188:Potassium; D002118:Calcium