NEUROACTIVE STEROIDS INDUCE GABA(A) RECEPTOR-MEDIATED DEPOLARIZING POSTSYNAPTIC POTENTIALS IN HIPPOCAMPAL CA1 PYRAMIDAL CELLS OF THE RAT

Citation
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
Citations number
24
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences
ISSN journal
0953-816X
Volume
10
Issue
9
Year of publication
1998
Pages
2880 - 2886
Database
ISI
SICI code
0953-816X(1998)10:9<2880:NSIGRD>2.0.ZU;2-C
Abstract
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-.