ROLE OF HCO3- IONS IN DEPOLARIZING GABA-A RECEPTOR-MEDIATED RESPONSESIN PYRAMIDAL CELLS OF RAT HIPPOCAMPUS

1. Activation of GABA(A) receptors can produce both hyperpolarizing an d depolarizing responses in CA1 pyramidal cells. The hyperpolarizing r esponse is mediated by a Cl- conductance, but the ionic basis of the d epolarizing response is not clear. We compared the GABA(A) receptor-me diated depolarizations induced by synaptically released gamma-aminobut yric acid [GABA; depolarizing inhibitory postsynaptic potentials (dIPS Ps)] with those produced by exogenous GABA (depolarizing GABA response s). Short trains of high-frequency (200 Hz) stimuli were used to gener ate dIPSPs. We found that dIPSPs generated by trains of stimuli and de polarizing responses to exogenous GABA were accompanied by a conductan ce increase and had a similar reversal potential, indicating a similar ionic basis for both responses. 2. We wished to determine whether an HCO3- current contributed to the GABA(A)-mediated depolarizations. We found that dIPSPs and depolarizing GABA responses were sensitive to pe rfusion with HCO3--free medium. Interpretation of these data was compl icated by the mixed nature of the responses: dIPSPs were invariably ac companied by conventional, Cl--mediated fast hyperpolarizing IPSPs (fI PSPs), and response to exogenous GABA usually consisted of biphasic hy perpolarizing and depolarizing responses. However, it was sometimes po ssible to elicit responses to GABA that appeared purely depolarizing ( monophasic depolarizing GABA responses). 3. We analyzed monophasic dep olarizing GABA responses and found no change in reversal potential whe n slices were perfused with HCO3--free medium. We also made whole-cell recordings from CA1 pyramidal cells, attempting to reduce [HCO3-]i, a nd compared the reversal potential for monophasic depolarizing GABA re sponses with similar responses recorded with fine intracellular microe lectrodes. We found no difference in reversal potential. We also exami ned effects of the carbonic anhydrase inhibitor acetazolamide (ACTZ) o n depolarizing GABA responses. ACTZ reduced these responses but did no t change their reversal potential. 4. Effects of HCO3--free medium wer e not specific to GABA(A) receptor-mediated responses. GABA(B) recepto r-mediated slow IPSPs (sIPSPs) were also reduced, as were excitatory p ostsynaptic potentials (EPSPs). Analyses of field potentials and spont aneous fIPSPs suggested a decrease in presynaptic excitability during perfusion with HCO3--free medium. In addition, pyramidal cells showed decreased input resistance when perfused with HCO 3--free medium. 5. T he sensitivity of GABA(A) receptor-mediated depolarizations to HCO3--f ree medium can be explained by a decrease in presynaptic excitability and an increased resting conductance in postsynaptic neurons. Reduced presynaptic excitability and resting input resistance are also likely causes of the reduction in fast IPSPs, slow IPSPs, and EPSPs in HCO3-- free medium. We suggest that these nonspecific effects of HCO3--free m edium may be a consequence of an extracellular acidification. These da ta do not provide convincing evidence for involvement of an HCO3- cond uctance in the generation of dIPSPs and depolarizing GABA responses.