Modulation of mammalian dendritic GABA(A) receptor function by the kinetics of Cl- and HCO3- transport

J Physiol. 1999 Sep 15;519 Pt 3(Pt 3):693-712. doi: 10.1111/j.1469-7793.1999.0693n.x.


1. During prolonged activation of dendritic GABAA receptors, the postsynaptic membrane response changes from hyperpolarization to depolarization. One explanation for the change in direction of the response is that opposing HCO3- and Cl- fluxes through the GABAA ionophore diminish the electrochemical gradient driving the hyperpolarizing Cl- flux, so that the depolarizing HCO3- flux dominates. Here we demonstrate that the necessary conditions for this mechanism are present in rat hippocampal CA1 pyramidal cell dendrites. 2. Prolonged GABAA receptor activation in low-HCO3- media decreased the driving force for dendritic but not somatic Cl- currents. Prolonged GABAA receptor activation in low-Cl- media containing physiological HCO3- concentrations did not degrade the driving force for dendritic or somatic HCO3- gradients. 3. Dendritic Cl- transport was measured in three ways: from the rate of recovery of GABAA receptor-mediated currents between paired dendritic GABA applications, from the rate of recovery between paired synaptic GABAA receptor-mediated currents, and from the predicted vs. actual increase in synaptic GABAA receptor-mediated currents at progressively more positive test potentials. These experiments yielded estimates of the maximum transport rate (vmax) for Cl- transport of 5 to 7 mmol l-1 s-1, and indicated that vmax could be exceeded by GABAA receptor-mediated Cl- influx. 4. The affinity of the Cl- transporter was calculated in experiments in which the reversal potential for Cl- (ECl) was measured from the GABAA reversal potential in low-HCO3- media during Cl- loading from the recording electrode solution. The calculated KD was 15 mM. 5. Using a standard model of membrane potential, these conditions are demonstrated to be sufficient to produce the experimentally observed, activity-dependent GABA(A) depolarizing response in pyramidal cell dendrites.

Publication types

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

MeSH terms

  • Animals
  • Antiporters / metabolism*
  • Bicarbonates / metabolism*
  • Chloride-Bicarbonate Antiporters
  • Chlorides / metabolism*
  • Dendrites / metabolism*
  • Evoked Potentials
  • Hippocampus / metabolism
  • Kinetics
  • Models, Neurological
  • Rats
  • Receptors, GABA-A / physiology*
  • Synapses / metabolism


  • Antiporters
  • Bicarbonates
  • Chloride-Bicarbonate Antiporters
  • Chlorides
  • Receptors, GABA-A