Run down of GABAergic depolarization during metabolic inhibition of rat hippocampal CA1 neurons

We investigated the effects of metabolic inhibition on both the shift in the equilibrium potential for Cl^- (E_Cl) and the run down of GABA_A receptor responses, using nystatin- and gramicidin-perforated patch-clamp recordings from rat hippocampal CA1 neurons. Metabolic inhibition with NaCN decreased outward GABAergic currents while increasing inward GABAergic currents. E_Cl showed a positive shift almost immediately after metabolic poisoning. This shift always occurred prior to GABA receptor run down, which was observed as decreases in whole cell conductance during application of a GABA_A receptor agonist. The results indicate that GABAergic responses tend to become depolarizing during metabolic inhibition and the run down of the GABAergic response may therefore be neuroprotective against excitotoxicity. Furthermore the results illustrate the importance of considering both changes in receptor function and current driving force, and their temporal relationship, in order to understand the physiological response of the GABAergic system during metabolic stress.