M. Burg et al., NEUROACTIVE STEROIDS INDUCE GABA(A) RECEPTOR-MEDIATED DEPOLARIZING POSTSYNAPTIC POTENTIALS IN HIPPOCAMPAL CA1 PYRAMIDAL CELLS OF THE RAT, European journal of neuroscience, 10(9), 1998, pp. 2880-2886
Intracellular recordings were performed in area CA1 pyramidal cells of
rat hippocampal slices to determine the effects of certain steroids o
n inhibitory postsynaptic potentials/currents (IPSP/Cs) mediated by GA
BA(A) receptors. Following application of the steroids 5 alpha-pregnan
-3 alpha,21-diol-20-one (5 alpha-THDOC), alphaxalone and 5 beta-pregna
n-3 alpha-ol-20-one (pregnanolone) hyperpolarizing PSPs developed into
biphasic responses consisting of an early hyperpolarizing and a late
depolarizing PSP sequence. Steroid-induced depolarizing PSPs could be
elicited in the presence of antagonists to non-NMDA, NMDA, and GABA(B)
receptors, indicating that these receptor types do not contribute sig
nificantly to the initiation of these responses. Depolarizing PSPs wer
e completely blocked by both GABA(A) receptor antagonists bicuculline
and t-butylbicyclophosphorothionat (TBPS) providing evidence for their
mediation by GABA(A) receptors. The reversal potential of steroid-ind
uced late inward PSCs, measured in single-electrode voltage clamp, was
-29.9 +/- 5.3 mV, whereas the early outward current, which correspond
ed to the early hyperpolarizing component of PSPs, reversed at -68.2 /- 1.5 mV. Depolarizing PSPs and late inward PSCs were sensitive to re
duction of extracellular [HCO3-] and block of carbonic anhydrase by ap
plication of acetazolamide. The results suggest that certain neuroacti
ve steroids can induce GABA(A) receptor-mediated depolarizing PSPs, wh
ich are dependent on HCO3-.