Cell-type-specific GABA responses and chloride homeostasis in the cortex and amygdala

The GABA responses of fast-spiking (FS) interneurons and regular-spiking (R S) principal cells were studied using whole cell and perforated-patch recor dings in slices of the basolateral amygdala, neo-, and perirhinal cortex. I n these three areas, responses to exogenous and synaptically released GABA were abolished by GABA(A) receptor antagonists in FS cells but also include d a GABA(B) component in RS cells. Moreover, E-GABAA of FS and RS cells dif fered from the calculated E-Cl (-61 mV), but in opposite direction (FS, -54 mV; RS, -72 mV). This was not due to a differential dialysis of FS and RS cells by the pipette solution because the discrepancy persisted when record ings were obtained with the perforated-patch-clamp technique, using the cat ion-selective ionophore gramicidin. Moreover, pharmacological inhibition of cation-chloride cotransporters revealed that the differing E-GABAA of FS a nd RS neurons arises from cell-type-specific chloride homeostatic mechanism s. Indeed, the prevalent regulators of the intracellular chloride concentra tion are cotransporters that accumulate chloride in FS cells and extrude ch loride in RS neurons. Thus, our results suggest that in the basolateral amy gdala as well as in the parietal and perirhinal cortices, FS interneurons a re more excitable than principal cells not only by virtue of their dissimil ar electroresponsive properties but also because they express a different c omplement of GABA receptors and chloride homeostatic mechanisms.