Using whole cell patch-clamp recordings, we examined the effect of colchicine, a microtubule disrupter, on the properties of glycine receptors (GlyRs) in cultured spinal cord neurons. Confocal microscopy revealed that colchicine treatment effectively altered microtubule bundles and neuronal morphology. Application of colchicine via the culture media or the patch-pipette, however, did not affect the whole cell current rundown (73 +/- 6% of control after 1 h), the sensitivity of the GlyR to glycine (EC(50) = 29 +/- 1 microM), or strychnine inhibition (47 +/- 5% of control after 100 nM strychnine). On the other hand, colchicine dialyzed for 25 min via the patch pipette selectively reduced the quantal amplitude of spontaneous glycinergic miniature inhibitory postsynaptic currents (mIPSCs) to 68 +/- 5% of control. This effect was specific for GlyRs since synaptic events mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and GABA(A) receptors were unchanged. In conclusion, this study indicates that microtubules can regulate the function of GlyRs involved in inhibitory synaptic transmission.