Effects of the neuropeptide thyrotropin-releasing hormone on GABAergic synaptic transmission of CA1 neurons of the rat hippocampal slice during hypoxia.
Because thyrotropin-releasing hormone (TRH) has been suggested to improve recovery of brain neurons from hypoxia, which strongly impairs GABAergic synaptic transmission, the present electrophysiological study used intracellular recording from CA1 neurons of the rat hippocampal slice to examine the cellular mechanisms underlying this phenomenon. Hypoxia induced by superfusion with a medium devoid of oxygen evoked typical membrane hyperpolarization, fall in input resistance, and strong depression of monosynaptic, GABAA receptor-mediated fast inhibitory postsynaptic potentials (IPSPs). The depression of fast IPSPs during hypoxia was found to be due to a combination of factors such as shift in the IPSP reversal potential and membrane hyperpolarization. GABAB receptor-mediated slow IPSPs were comparatively less sensitive to hypoxia. TRH (10 microM), applied 1 min prior to hypoxia, selectively accelerated recovery of membrane potential and delayed return of fast IPSPs to control amplitude without changing the mechanisms responsible for depression of GABAergic transmission. In conclusion, despite a slower recovery of IPSPs, TRH facilitated earlier return of neuronal excitability after the hypoxic period.
Barbieri
M
M
Biophysics Sector, International School for Advanced Studies (S.I.S.S.A.), Trieste, Italy.
Nistri
A
A
D000818:Animals; D004353:Drug Evaluation, Preclinical; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000473:pathology; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D013973:Thyrotropin-Releasing Hormone