Role of HCO3/- ions in depolarizing GABA(A) receptor-mediated responses in pyramidal cells of rat hippocampus

L. M. Grover, N. A. Lambert, P. A. Schwartzkroin, T. J. Teyler

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97 Scopus citations

Abstract

1. Activation of GABA(A) receptors can produce both hyperpolarizing and depolarizing responses in CA1 pyramidal cells. The hyperpolarizing response is mediated by a Cl- conductance, but the ionic basis of the depolarizing response is not clear. We compared the GABA(A) receptor-mediated depolarizations induced by synaptically released γ-aminobutyric acid [GABA; depolarizing inhibitory postsynaptic potentials (dIPSPs)] with those produced by exogenous GABA (depolarizing GABA responses). Short trains of high- frequency (200 Hz) stimuli were used to generate dIPSPs. We found that dIPSPs generated by trains of stimuli and depolarizing responses to exogenous GABA were accompanied by a conductance 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 perfusion with HCO3/--free medium. Interpretation of these data was complicated by the mixed nature of the responses: dIPSPs were invariably accompanied by conventional, Cl--mediated fast hyperpolarizing IPSPs (fIPSPs), and response to exogenous GABA usually consisted of biphasic hyperpolarizing and depolarizing responses. However, it was sometimes possible to elicit responses to GABA that appeared purely depolarizing (monophasic depolarizing GABA responses). 3. We analyzed monophasic depolarizing GABA responses and found no change in reversal potential when slices were perfused with HCO3/--free medium. We also made whole-cell recordings from CA1 pyramidal cells, attempting to reduce [HCO3/-](i), and compared the reversal potential for monophasic depolarizing GABA responses with similar responses recorded with fine intracellular microelectrodes. We found no difference in reversal potential. We also examined effects of the carbonic anhydrase inhibitor acetazolamide (ACTZ) on depolarizing GABA responses. ACTZ reduced these responses but did not change their reversal potential. 4. Effects of HCO3/--free medium were not specific to GABA(A) receptor-mediated responses. GABA(B) receptor-mediated slow IPSPs (sIPSPs) were also reduced, as were excitatory postsynaptic potentials (EPSPs). Analyses of field potentials and spontaneous fIPSPs suggested a decrease in presynaptic excitability during perfusion with HCO3/--free medium. In addition, pyramidal cells showed decreased input resistance when perfused with HCO3/--free medium. 5. The sensitivity of GABA(A) receptor-mediated depolarizations to HCO3/--free 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 medium may be a consequence of an extracellular acidification. These data do not provide convincing evidence for involvement of an HCO3/- conductance in the generation of dIPSPs and depolarizing GABA responses.

Original languageEnglish (US)
Pages (from-to)1541-1555
Number of pages15
JournalJournal of Neurophysiology
Volume69
Issue number5
DOIs
StatePublished - Jan 1 1993
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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