Noninvasive measurements of the membrane potential and GABAergic action inhippocampal interneurons

Neurotransmitters affect the membrane potential (V-m) of target cells by mo dulating the activity of receptor-linked ion channels. The direction and am plitude of the resulting transmembrane current depend on the resting level of V-m and the gradient across the membrane of permeant ion species. V-m, i n addition, governs the activation state of voltage-gated channels. Knowled ge of the exact level of V-m is therefore crucial to evaluate the nature of the neurotransmitter effect. However, the traditional methods to measure V -m, with microelectrodes or the whole-cell current-clamp technique, have th e drawback that the recording pipette is in contact with the cytoplasm, and dialysis with the pipette solution alters the ionic composition of the int erior of the cell. Here we describe a novel technique to determine the V-m of an intact cell from the reversal potential of K+ currents through a cell -attached patch, Applying the method to interneurons in hippocampal brain s lices yielded more negative values for V-m than subsequent whole-cell curre nt-clamp measurements from the same cell, presumably reflecting the develop ment of a Donnan potential between cytoplasm and pipette solution in the wh ole-cell mode. Cell-attached V-m measurements were used to study GABAergic actions in intact CA1 interneurons. In 1- to 3-week-old rats, bath-applied GABA inhibited these cells by stabilizing V-m at a level depending on contr ibutions from both GABA(A) and GABA(B) components. In contrast, in 1- to 4- d-old animals, only GABA(A) receptors were activated resulting in a depolar izing GABA response.