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Neuroactive steroids induce GABA A receptor‐mediated depolarizing postsynaptic potentials in hippocampal CA1 pyramidal cells of the rat
Author(s) -
Burg M.,
Heinemann U.,
Schmitz D.
Publication year - 1998
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1998.00297.x
Subject(s) - neuroactive steroid , depolarization , gabaa receptor , bicuculline , inhibitory postsynaptic potential , chemistry , postsynaptic potential , reversal potential , neuroscience , pregnanolone , endocrinology , medicine , biophysics , receptor , patch clamp , biology , biochemistry
Intracellular recordings were performed in area CA1 pyramidal cells of rat hippocampal slices to determine the effects of certain steroids on inhibitory postsynaptic potentials/currents (IPSP/Cs) mediated by GABA A receptors. Following application of the steroids 5α‐pregnan‐3α,21‐diol‐20‐one (5α‐THDOC), alphaxalone and 5β‐pregnan‐3α‐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 significantly to the initiation of these responses. Depolarizing PSPs were 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‐induced late inward PSCs, measured in single‐electrode voltage clamp, was −29.9 ± 5.3 mV, whereas the early outward current, which corresponded to the early hyperpolarizing component of PSPs, reversed at −68.2 ± 1.5 mV. Depolarizing PSPs and late inward PSCs were sensitive to reduction of extracellular [HCO 3 – ] and block of carbonic anhydrase by application of acetazolamide. The results suggest that certain neuroactive steroids can induce GABA A receptor‐mediated depolarizing PSPs, which are dependent on HCO 3 – .