Extracellular pH changes during spreading depression and cerebral ischemia: mechanisms of brain pH regulation.
We have examined the extracellular pH (pHe) during spreading depression and complete cerebral ischemia in rat parietal cortex utilizing double-barrelled H+ liquid ion exchanger microelectrodes. The baseline pHe of the parietal cortex was 7.33 at a mean arterial PCO2 of 38 mm Hg. Following spreading depression and cerebral ischemia, highly reproducible triphasic changes in pHe occurred, which were intimately related to the negative deflection in tissue potential (Ve). The changes in pHe for spreading depression (n = 23) were a small initial acidic shift, beginning before the rapid change in Ve, followed by a rapid transient alkaline shift of 0.16 pH units, the onset of which coincided with the negative deflection in Ve. A prolonged acidic shift of 0.42 pH units then occurred. The maximal decrease in pHe was to 6.97 and the mean duration of the triphasic pHe change was 7.8 min. The lactate concentration in brain cortex increased from baseline 1.2 mM to 7.0 mM (n = 6) during the maximal acidic change in spreading depression. In addition, lactate levels correlated well with resolution of the pHe changes during spreading depression. The triphasic pHe changes following complete cerebral ischemia were an initial acidic shift of 0.43 pH units which developed over 2 min, then an alkaline shift of 0.10 pH units coincident with the negative deflection in Ve, and a final acidic shift of 0.26 pH units. The terminal pHe was 6.75. Superfusion of the cortex with inhibitors of carbonic anhydrase (acetazolamide), Na+/H+ counter transport (amiloride), and Cl-/HCO-3 countertransport (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid) altered the triphasic pHe changes in a similar fashion for both spreading depression and cerebral ischemia, providing insights into the pHe regulatory mechanisms in mammalian brain.
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000086:Acetazolamide / Q000494:pharmacology; D000136:Acid-Base Equilibrium; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D006706:Homeostasis; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000378:metabolism; D008297:Male; D008839:Microelectrodes; D010296:Parietal Lobe / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D007773:Lactates; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D000584:Amiloride; D000086:Acetazolamide; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid