Colchicine competitively antagonizes glycine receptors expressed in Xenopus oocytes

Ligand-gated ion channel association with the cytoskeleton may play an important role in receptor distribution and function. However, the microtubule depolymerizing agent, colchicine, has inhibitory effects on glycine receptors that are independent of microtubule depolymerization. The actions of colchicine and other microtubule-modifying drugs were examined on glycine α1 and α2 receptors expressed in Xenopus oocytes. The potency of colchicine was much greater in α2 than α1 receptors, with IC₅₀s of ~64 and 324 μM in α2 and α1 receptors, respectively. Colchicine inhibition of receptor function was instantaneous. Pre-incubation with colchicine failed to enhance its inhibition, and washout of colchicine's inhibition could be observed in 30 s. Incubation of oocytes on ice for 2 h to depolymerize microtubules failed to alter colchicine's antagonism of glycine receptors. Taxol, a microtubule polymerizing agent, and nocodazole, a depolymerizing drug, had no effect on receptor function when co-applied with glycine. The antagonism of glycine-mediated currents by colchicine (100-600 μM) was competitive. Thus, the action of colchicine at the agonist recognition site of the glycine receptor suggest that this drug should be used with care whne studying microtubule-associated changes in ligand-gated ion channel function.