Postsynaptic fall in intracellular pH and increase in surface ph caused by efflux of formate and acetate anions through GABA-gated channels in crayfish muscle fibres

Spontaneous Network Events Driven by Depolarizing GABA Action in Neonatal Hippocampal Slices are Not Attributable to Deficient Mitochondrial Energy Metabolism

“…The more pronounced decrease in GDPs with 5 mM propionate can be explained on the basis of the differences in the pK a values of the weak acids used. With an identical total concentration of the two weak acids at a pH of ϳ7.4, the membrane-permeable protonated form of propionate (pK a , 4.87) is present at ϳ10ϫ higher concentration than that of lactate (pK a , 3.86), which leads to a much higher initial rate of net influx of H ϩ (Roos and Boron, 1981;Mason et al, 1990). In agreement with this, a rapid and pronounced reduction of GDP frequency (to 37.2 Ϯ 8%, n ϭ 6) ( Fig.…”

The role of bicarbonate in GABAA receptor‐mediated IPSPs of rat neocortical neurones.

“…A further complication which precluded the use of ammonia in the present work is its capability to inhibit K+-Cl-co-transport (Aickin et al 1982;Thompson et al 1988 b). Lactate was chosen in the present experiments because it permeates cell membranes in its protonated form by both passive and facilitated diffusion (Spencer & Lehninger, 1976;De Hemptinne et al 1983;Mason et al 1990). Both mechanisms promote a fall in pH1 upon exposure of a cell to a lactate-containing solution.…”

“…We examined the effects of a membrane-permeant weak base (trimethylamine; TriMA) and of a weak acid (lactate) at a constant extracellular Clconcentration. Application of TriMA is expected to produce a rise in pHi and, hence, in intracellular HC03-, while lactate ought to have an opposite effect (Roos & Boron, 1981;Eisner, Kenning, O'Neill, Pocock, Richards & Valdeolmillos, 1989;Mason, Mattsson, Pasternack, Voipio & Kaila, 1990). The present observations are consistent with a significant contribution of HC03-to the generation of GABAA receptormediated IPSPs in the mammalian neocortex.…”

Extracellular alkalinization evoked by GABA and its relationship to activity‐dependent pH shifts in turtle cerebellum.

“…in the vertebrate brain can be similarly modulated by a GABA-gated HC03-efflux. This conclusion is based on the following evidence: (1) the GABA-evoked alkaline shift was blocked by picrotoxin and was mimicked by isoguvacine, but was never elicited by baclofen, indicating that it was mediated via GABAA receptors; (2) the response was consistently blocked in the nominal absence of HCO3-, whereas evoked field potentials were not significantly altered; (3) the alkaline shift persisted when synaptic transmission was abolished in nominally zero-Ca2+, high-Mg2+ media, indicating that it was a direct consequence of the gating of GABAA receptor channels; (4) formate ions, which can permeate the GABAA receptor channel (Bormann et al 1987;Mason et al 1990) were able to substitute for HC03-, giving rise to a GABA-evoked alkaline shift in HEPESbuffered media. Alternatively, an alkaline shift could arise due to a decrease in extracellular acid production.…”

“…In a total of seven trials in these media, carried out in four preparations, superfusion of 1 mM-GABA produced an average alkaline shift of 0-051 +0-017 pH units. Effect offormate substitution in HC03--free media Among the weak bases which can pass through the GABAA receptor-channel complex, HC03-and formate have the largest permeabilities (Inomata, Oomura, Akaike & Edwards, 1986;Bormann et al 1987;Kaila and Voipio, 1987;Kaila et al 1989;Mason, Mattsson, Pasternack, Voipio & Kaila, 1990 , 1981). Accordingly, the electrochemical gradient for formate will be outward, and addition of GABA would be expected to cause a formate efflux and an extracellular alkaline shift (Mason et al 1990).…”