PT - JOURNAL ARTICLE AU - Dieter K. Meyer AU - Claudia Olenik AU - Fred Hofmann AU - Holger Barth AU - Jost Leemhuis AU - Ina Brünig AU - Klaus Aktories AU - Wolfgang Nörenberg TI - Regulation of Somatodendritic GABA<sub>A</sub> Receptor Channels in Rat Hippocampal Neurons: Evidence for a Role of the Small GTPase Rac1 AID - 10.1523/JNEUROSCI.20-18-06743.2000 DP - 2000 Sep 15 TA - The Journal of Neuroscience PG - 6743--6751 VI - 20 IP - 18 4099 - http://www.jneurosci.org/content/20/18/6743.short 4100 - http://www.jneurosci.org/content/20/18/6743.full SO - J. Neurosci.2000 Sep 15; 20 AB - The role of the cytoskeleton in the activity of GABAAreceptors was investigated in cultured hippocampal neurons. Receptor currents were measured with the whole-cell patch-clamp technique during repetitive stimulation with 1 μm muscimol. After destruction of the microtubular system with nocodazol, muscimol-induced currents showed a rundown by 78%. A similar rundown was observed when actin fibers were destroyed with latrunculin B or C2 toxin of Clostridium botulinum. Because the small GTPases of the Rho family RhoA, Rac1, and Cdc42 are known to control the organization of actin fibers, we investigated their possible involvement. Inactivation of the GTPases with clostridial toxins, as well as intracellular application of recombinant Rho GTPases, indicated that active Rac1 was necessary for full GABAA receptor activity. Immunocytochemical labeling of the receptors showed that the disappearance of receptor clusters in the somatic membrane as induced by muscimol stimulation was enhanced by Rac1 inactivation. It is suggested that Rac1 participates in the regulation of GABAAreceptor clustering and/or recycling.