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 neuronal excitability. However, the mechanism whereby a change in CO2 partial pressure (PCO2) leads to changes in neural excitability is not known. We have studied this phenomenon in rat hippocampal slices using double-barrelled microelectrodes for simultaneous recording of field excitatory postsynaptic potentials (EPSPs) and extracellular pH in stratum radiatum of area CA1. A drop in PCO2 from the control level, 36 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%. Despite the stable extracellular alkalosis, the EPSP reverted back to its original level within 10 min. Switching back to 36 mmHg PCO2 restored the original extracellular pH and caused a transient decrease in the EPSP slope. Pharmacological blockade of NMDA receptor and/or GABAA receptor had no influence on the effects of CO2. An increase in PCO2 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 indicate that the CO2-induced changes in neuronal excitability were not caused by changes in extracellular pH but they might have been mediated by changes in intracellular pH. Indeed, exposing the slices to the permeant weak base, trimethylamine (20 mM), which is known to produce a rise in intracellular pH, increased the EPSP slope by 50-70%. Application of 20 mM propionate (a permeant weak acid) decreased the EPSP slope by 40-60%. We conclude that the transient changes in the EPSP seen in response to changes in PCO2 are mediated by in intracellular pH.