Inhibition of M-type K+ current by linopirdine, a neurotransmitter-release enhancer, in NG108-15 neuronal cells and rat cerebral neurons in culture.

The effect of linopirdine, a neurotransmitter-release enhancer, on the M-type K+-current, IK(M), was examined in NGPM1-27 cells, mouse neuroblastomaxrat glioma NG108-15 cells transformed to express m1-muscarinic acetylcholine (ACh) receptors, using the nystatin-perforated patch-recording mode under voltage-clamp conditions. The application of linopirdine induced the inward current associated with an inhibition of IK(M), which mimics an excitatory part of the ACh-induced responses in NGPM1-27 cells. The affinity of linopirdine for the inhibition of IK(M) was 24.7 microM in NGPM1-27 cells. In the presence of linopirdine, ACh failed to evoke a further inward current, but ACh still elicited an outward current, thus suggesting that the Ca2+-dependent K+ current is rather insensitive to linopirdine. Linopirdine also inhibited another voltage-gated potassium current (IK(V)) at the concentration of 72.3 microM. Finally, the inhibitory effect of linopirdine on IK(M) was confirmed in pyramidal neurons acutely dissociated from the rat cerebral cortex at 35.8 microM. The results suggest that linopirdine is thus considered to be an inhibitor of some type of K+ channels in both NGPM1-27 cells and the rat cerebral neurons.