Regulation of somatodendritic GABA(A) receptor channels in rat hippocampalneurons: Evidence for a role of the small GTPase Rac1

The role of the cytoskeleton in the activity of GABA(A) receptors was inves tigated in cultured hippocampal neurons. Receptor currents were measured wi th the whole-cell patch-clamp technique during repetitive stimulation with 1 mu M muscimol. After destruction of the microtubular system with nocodazo l, muscimol-induced currents showed a rundown by 78%. A similar rundown was observed when actin fibers were destroyed with latrunculin B or C2 toxin o f Clostridium botulinum. Because the small GTPases of the Rho family RhoA, Rac1, and Cdc42 are known to control the organization of actin fibers, we i nvestigated their possible involvement. Inactivation of the GTPases with cl ostridial toxins, as well as intracellular application of recombinant Rho G TPases, indicated that active Rac1 was necessary for full GABA(A) receptor activity. Immunocytochemical labeling of the receptors showed that the disa ppearance of receptor clusters in the somatic membrane as induced by muscim ol stimulation was enhanced by Rac1 inactivation. It is suggested that Rac1 participates in the regulation of GABA(A) receptor clustering and/or recyc ling.