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Mechanisms of hyperthermia‐induced depression of GABAergic synaptic transmission in the immature rat hippocampus
Author(s) -
Qu Lintao,
Leung L. Stan
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05576.x
Subject(s) - neurotransmission , hyperthermia , adenylyl cyclase , inhibitory postsynaptic potential , hippocampus , forskolin , neuroscience , gabaergic , biology , chemistry , endocrinology , medicine , receptor , stimulation
Clinical observations and experimental studies have shown that hyperthermia can provoke febrile seizures, which are the most common type of pathological brain activity in children. We previously demonstrated that hyperthermia produced a depression of GABAergic neurotransmission in the hippocampus of immature rats in vitro . To investigate the possible mechanisms through which hyperthermia may modulate GABAergic neurotransmission in the hippocampus, whole‐cell voltage clamp recordings were performed on CA1 pyramidal neurons in the immature rat brain slices. We found that hyperthermia (38.4–40°C) when compared with baseline temperature of 32°C reduced the frequency of both spontaneous inhibitory post‐synaptic currents (sIPSCs) and miniature IPSCs (mIPSCs). Also, hyperthermia decreased the amplitudes of mIPSCs and reduced the mIPSC decay time constants and charge transfer. Non‐stationary noise analysis of mIPSCs suggested that the number of open post‐synaptic receptors but not single channel conductance was reduced during hyperthermia. Activation of adenylyl cyclase with forskolin prevented, whereas protein kinase A inhibitor N ‐(2‐[ p ‐bromocinnamylamino]ethyl)‐5‐isoquinolinesulfonamide potentiated, the hyperthermia (40°C)‐induced depression of evoked IPSCs (evIPSCs). But protein kinase C activator phorbol 12, 13‐dibutyrate (PDBu) did not significantly affect this depression of evIPSCs induced by hyperthermia. Furthermore, hyperthermia‐induced depression of evIPSCs was attenuated by 4‐aminopyridine, but not by BaCl 2 . These results suggest that hyperthermia reduces GABA release from pre‐synaptic terminals, in part by blocking the adenylyl cyclase–protein kinase A signaling pathway and activating pre‐synaptic 4‐aminopyridine‐sensitive K + channels. Also, the changes in amplitude and decay time constant of the mIPSCs may suggest that hyperthermia also decreases post‐synaptic GABA A receptor function.