Presynaptic action of the neurosteroid pregnenolone sulfate on inhibitory transmitter release in cultured hippocampal neurons.
The effects of the neurosteroid pregnenolone sulfate (PS) were studied in 3- to 9-week-old hippocampal cultures from neonatal rats. Cells were voltage clamped using CsCl filled electrodes, while action potentials and excitatory glutamatergic currents were abolished by superfusing with a combination of tetrodotoxin, 6-cyano-7-nitroquinoxaline (CNQX) and 2-amino-5-phosphonopentanoic acid (AP-5). Under these conditions spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs) were seen as inward currents at a holding potential of -70 mV. Their amplitude distributions were skewed without clearly detectable peaks. PS at 1-50 microM concentrations decreased the frequency of sIPSCs, with 1 microM being the most effective concentration. The effect appeared after 10-15 min of steroid application and the magnitude of the reduction increased during the early wash period. No recovery of sIPSC frequency was found after 30 min of washing with steroid-free medium. sIPSC amplitudes were not significantly changed at the time the effect of PS on sIPSC frequency was observed. The slow onset of this effect and its duration suggest a novel presynaptic action of the neurosteroid PS on GABAergic inhibition in the mammalian brain.
Teschemacher
A
A
Department of Neurobiology, Harvard Medical School, Boston, MA, USA. anja.teschemacher@bristol.ac.uk
Kasparov
S
S
Kravitz
E A
EA
Rahamimoff
R
R
D000818:Animals; D002478:Cells, Cultured; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011284:Pregnenolone / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects*; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
C018370:pregnenolone sulfate; D005680:gamma-Aminobutyric Acid; D011284:Pregnenolone