Bicarbonate and ammonia changes in brain during spreading depression

Abstract

An alkaline, followed by an acid-going transient, characterizes acid-base changes in the interstitial space during spreading depression in a variety of brain structures. In rat, such changes are associated with a significant rise in brain lactate content. How brain proton buffers behave during spreading depression is unknown. Techniques to significantly improve the response time of gas permeable membrane semnimicroelectrodes for carbon dioxide and ammonia are reported. Measurements with such electrodes, when coupled to measurements of hydrogen ion concentration (from microelectrodes), permit rapid changes to be determined in bicarbonate concentration or ammonia and ammonium ion concentration, respectively. Bicarbonate concentration fell from 30 ± 1 (n = 16) to 14 ± 1 mM (n = 16) during spreading depression. On the other hand, ammonia concentration rose from 2.3 ± 0.1 to 4.4 ± 0.3 μM (n = 17) while ammonium ion concentration rose from 116 ± 11 (n = 17) to 382 ± 30 μM (n = 17) during spreading depression. Bicarbonate changes probably reflect titration of brain bicarbonate stores by accumulated lactic acid. Similar physicochemical changes do not explain the rise in ammonia and ammonium ion concentrations. Instead, elevation of the latter can only result from an increase in ammonia content of the interstitial space.

Methionine Sulfoximine, a Glutamine Synthetase Inhibitor, Attenuates Increased Extracellular Potassium Activity during Acute Hyperammonemia

“…Potassium channels are permeable to ammonium ions (Hille, 1992); however, permeability to ammonium ions is approximately an or der of magnitude less than K+ permeability when both ions are present in similar concentrations (Blatz and Magleby, 1984;Hille, 1973). Hindfelt (1975) (Kraig and Cooper, 1987), which is probably intermediate between plasma and intracellular concen trations (Hindfelt, 1972(Hindfelt, , 1974 (Walz and Hertz, 1983). If a similar K+ influx occurs in astro cytes during hyperammonemia, the normal dissipative K+ routes through the purported network of astrocyte gap junctions (Robinson et aI., 1993) could become over loaded, thereby exacerbating glutamine-dependent astro cyte swelling.…”

“…At a plasma [NH4 +] of 628 /-LmollL in the pres ent study, intracellular NH4 + is predicted to be about 1.3 mmol/L, a value that is lower than intracellular [K+] by at least two orders of magnitude and thus is expected to exert a negligible amount of competition with intracel lular [K+] for K+ efflux through K+ channels. The control value of extracellular [NH4 +] is reported to be 116 /-LmollL (Kraig and Cooper, 1987), which is probably intermediate between plasma and intracellular concen trations (Hindfelt, 1972(Hindfelt, , 1974 and Hertz, 1983). If a similar K+ influx occurs in astro cytes during hyperammonemia, the normal dissipative K+ routes through the purported network of astrocyte gap junctions (Robinson et aI., 1993) could become over loaded, thereby exacerbating glutamine-dependent astro cyte swelling.…”

Electrophysiological properties of rat CA1 pyramidal neurones in vitro modified by changes in extracellular bicarbonate.

“…10). and spreading depression, prior to which marked alkaline transients are observed (Kraig, Ferreira-Filho & Nicholson, 1983;Mutch & Hansen, 1984;Kraig & Cooper, 1987;Balestrino & Somjen, 1988 [Cl-1o (see Kazemi & Johnson, 1986).…”

“…10). effects may play a role in pathophysiological events associated with cerebral ischaemia or intense seizure activity, which provoke substantial falls in [HC03-]o0 and spreading depression, prior to which marked alkaline transients are observed (Kraig, Ferreira-Filho & Nicholson, 1983;Mutch & Hansen, 1984;Kraig & Cooper, 1987;Balestrino & Somjen, 1988). For reasons outlined in the Introduction, we chose to examine the effects of changing [HCO3-j0 on CAI pyramidal cell activity, accepting the fact that changes in [HCO3-j0 would inevitably affect pHo, [Ca2+]0 and (in our experimental protocol) [Cl-]O.…”

Neocortical spreading depression provokes the expression of c-fos protein-like immunoreactivity within trigeminal nucleus caudalis via trigeminovascular mechanisms

“…SD develops within cerebral cortex of animals and possibly humans (Avoli et al, 1991) in response to noxious stimuli. Single episodes are associated with dramatic changes in interstitial [K+], [H+], [Na'], [Ca*+], [Cll] (Nicholson and Kraig,198 l), and [HCO,-] (Kraig and Cooper, 1987), as well as in levels of glutamate, lactate (Krivanek, 196 1;Mutch and Hansen, 1984), and arachidonic acid and metabolites such as the prostaglandins (Lauritzen et al, 1990). In otherwise normal brain, ionic concentrations return to baseline by 3-4 min whereas elevated lactate and arachidonate levels persist for up to 10 min.…”