THE SMALL GTP-BINDING PROTEIN RHOA REGULATES A DELAYED RECTIFIER POTASSIUM CHANNEL

Tyrosine kinases activated by G protein-coupled receptors can phosphor ylate and thereby suppress the activity of the delayed rectifier potas sium channel Kv1.2. Using a yeast two-hybrid screen, we identified the small GTP-binding protein RhoA as a necessary component in this proce ss. Coimmunoprecipitation experiments confirmed that RhoA associates w ith Kv1.2. Electrophysiological analyses revealed that overexpression of RhoA markedly reduced the basal current generated by Kv1.2 expresse d in Xenopus oocytes. Furthermore, in 293 cells expressing Kv1.2 and m 1 muscarinic acetylcholine receptors, inactivating RhoA using C3 exoen zyme blocked the ability of mi receptors to suppress Kv1.2 current. Th erefore, these results demonstrate that RhoA regulates Kv1.2 activity and is a central component in the mechanism of receptor-mediated tyros ine kinase-dependent suppression of Kv1.2.