Modulation of decay kinetics and frequency of GABAA receptor-mediated spontaneous inhibitory postsynaptic currents in hippocampal neurons

Neuroscience. 1992 Jul;49(1):13-32. doi: 10.1016/0306-4522(92)90073-b.


Inhibitory postsynaptic currents mediated by spontaneous activation of GABAA receptors were studied using whole-cell voltage-clamp recordings in granule cells of the adult rat (postnatal day 60+) dentate gyrus in 400-microns-thick coronal half-brain slices maintained at 34-35 degrees C. The average amplitude of spontaneous inhibitory postsynaptic currents remained constant during a given recording period (i.e. no rundown was noted). The spontaneous currents had an average conductance between 200-400 pS, were mediated by Cl- flux through GABAA receptor/channels since they reversed at the Cl- equilibrium potential and were blocked by bicuculline or picrotoxin. Their mono-exponential decay time-constants (range: 4.2-7.2 ms) were prolonged by midazolam and pentobarbital in a dose-dependent manner. The effect of midazolam was reversed by the benzodiazepine receptor antagonist flumazenil (RO 15-1788) which, by itself, had no effect on the decay time-constant. The decay time-constant was also dependent on membrane voltage and on temperature. A 132-mV change in membrane potential produced an e-fold prolongation of the decay while the Q10 (between 22-37 degrees C) of the decay rate was 2.1. Within a given neuron, the frequency of spontaneous GABAergic events was remarkably constant over long time-periods, though the mean frequency among different cells showed large variability. Spontaneous miniature inhibitory postsynaptic currents also persisted under experimental conditions such as the presence of extracellular tetrodotoxin (1 microM), Cd2+ (200 microM) or lowered extracellular Ca2+/elevated Mg2+, which effectively abolished all stimulus-evoked GABAergic neurotransmission. The frequency of tetrodotoxin-resistant miniature events was increased by elevating extracellular K+ concentration and was diminished by the GABAB receptor agonist (-)baclofen only at a dose (50 microM) which was an order of magnitude larger than that required to depress stimulus-evoked responses. These findings are consistent with different mechanisms being responsible for the spontaneous and stimulus-evoked release of GABA from interneuron terminals and also identify pre- and postsynaptic modulatory factors of the endogenous, action-potential-independent, GABAergic neurotransmission as being important determinants of the excitability level of mammalian CNS neurons.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • Aging
  • Anesthetics, Local
  • Animals
  • Calcium Channels / drug effects
  • Calcium Channels / physiology
  • Evoked Potentials / drug effects
  • Flumazenil / pharmacology
  • Hippocampus / growth & development
  • Hippocampus / physiology*
  • Kinetics
  • Lidocaine / analogs & derivatives
  • Lidocaine / pharmacology
  • Mathematics
  • Meglumine / pharmacology
  • Membrane Potentials / drug effects
  • Midazolam / pharmacology
  • Models, Neurological
  • Neurons / drug effects
  • Neurons / physiology*
  • Pentobarbital / pharmacology
  • Probability
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / physiology*
  • Synapses / drug effects
  • Synapses / physiology*
  • Tetrodotoxin / pharmacology


  • Anesthetics, Local
  • Calcium Channels
  • Quinoxalines
  • Receptors, GABA-A
  • QX-314
  • Flumazenil
  • Tetrodotoxin
  • Meglumine
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • 2-Amino-5-phosphonovalerate
  • Lidocaine
  • Pentobarbital
  • Midazolam