The effect of simulated ischaemia on spontaneous GABA release in area CA1 of the juvenile rat hippocampus.
An early consequence of brain energy deprivation is an increase in the frequency of spontaneous inhibitory and excitatory postsynaptic currents (sIPSCs and sEPSCs), which may disrupt neural information processing. This increase in spontaneous transmitter release has been reported to occur in calcium-free solution and has been attributed either to calcium release from internal stores or to a direct effect of hypoxia on the transmitter release mechanism. Here we investigate the mechanism of the increase in sIPSC frequency that occurs in area CA1 of rat hippocampus during simulated ischaemia, by making patch-clamp recordings from CA1 pyramidal neurones. When recording in whole-cell mode, exposure to ischaemic solution increased the sIPSC frequency 30-fold (to 49 Hz) after 5 min, and doubled the sIPSC amplitude. Ischaemic sIPSCs were action potential independent, vesicular in origin and, contrary to the results of earlier studies which did not buffer extracellular calcium to a low level, dependent on extracellular calcium. The properties of the ischaemic sIPSCs were not affected by depleting intracellular stores of calcium or by blocking the neuronal GABA transporter GAT-1. Recording from neurones using gramicidin-perforated patch-clamping showed a 10-fold smaller, more transient increase in sIPSC frequency during ischaemia, with no change of sIPSC amplitude, suggesting that whole-cell clamp recording increases the ischaemia-induced sIPSC rate and amplitude by controlling the intracellular milieu.
Allen
Nicola J
NJ
Department of Physiology, University College London, Gower Street, London WC1E 6BT, UK.
Attwell
David
D
D000367:Age Factors; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005680:gamma-Aminobutyric Acid