EFFECTS OF CO2 ON EXCITATORY TRANSMISSION APPARENTLY CAUSED BY CHANGES IN INTRACELLULAR PH IN THE RAT HIPPOCAMPAL SLICE

It is generally known that hyperventilation produces an increase in ne uronal excitability. However, the mechanism whereby a change in CO2 pa rtial pressure (Pco(2)) leads to changes in neural excitability is not known. We have studied this phenomenon in rat hippocampal slices usin g double-barrelled microelectrodes for simultaneous recording of field excitatory postsynaptic potentials (EPSPs) and extracellular pH in st ratum radiatum of area CA1. A drop in Pco(2) from the control level, 3 6 mmHg to 7 mmHg, produced an increase in extracellular pH of 0.4-0.6 pH units and a transient increase in EPSP slope by about 20-30%. Despi te the stable extracellular alkalosis, the EPSP reverted back to its o riginal level within 10 min. Switching back to 36 mmHg Pco(2) restored the original extracellular pH and caused a transient decrease in the EPSP slope. Pharmacological blockade of NMDA receptor and/or GABA(A) r eceptor had no influence on the effects of CO2. An increase in Pco(2) to 145 mmHg led to a stable fall in extracellular pH by 0.6 units and to a transient 30-50% decrease in EPSP slope. The above results indica te that the CO2-induced changes in neuronal excitability were not caus ed by changes in extracellular pH but they might have been mediated by changes in intracellular pH. Indeed, exposing the slices to the perme ant weak base, trimethylamine (20 mM), which is known to produce a ris e in intracellular pH, increased the EPSP slope by 50-70%. Application of 20 mM propionate (a permeant weak acid) decreased the EPSP slope b y 40-60%. We conclude that the transient changes in the EPSP seen in r esponse to changes in Pco(2) are mediated by in intracellular pH.