Alteration of GABA(A) receptor function following gene transfer of the CLC-2 chloride channel

The effect of GABA(A) receptor activation varies from inhibition to excitation depending on the state of the transmembrane anionic concentration gradient (del(anion)). del(anion) was genetically altered in cultured dorsal root ganglion neurons via adenoviral vector-mediated expression of ClC-2, a Cl- channel postulated to regulate the Cl- concentration in neurons in which GABA(A) receptor activation is predominantly inhibitory. ClC-2 expression was verified by the presence of the appropriate mRNA, protein, and membrane conductance. ClC-2 expression resulted in a large negative shift in the Cl- equilibrium potential (E(Cl)) that attenuated the GABA-mediated membrane depolarization and prevented GABA(A) receptor-mediated action potentials. These results establish that gene transfer of transmembrane ion channels to neurons can be used to demonstrate their physiological function, and that del(anion) can be genetically manipulated to alter the function of neuronal GABA(A) receptors in situ.