INHIBITION OF M-TYPE K-RELEASE ENHANCER, IN NG108-15 NEURONAL CELLS AND RAT CEREBRAL NEURONS IN CULTURE( CURRENT BY LINOPIRDINE, A NEUROTRANSMITTER)

The effect of linopirdine, a neurotransmitter-release enhancer, on the M-type K+-current, I-K(M), was examined in NGPM1-27 cells, mouse neur oblastoma X rat glioma NG108-15 cells transformed to express ml-muscar inic acetylcholine (ACh) receptors, using the nystatin-perforated patc h-recording mode under voltage-clamp conditions. The application of li nopirdine induced the inward current associated with an inhibition of I-K(M), which mimics an excitatory part of the ACh-induced responses i n NGPM1-27 cells. The affinity of linopirdine for the inhibition of I- K(M) was 24.7 mu M in NGPM1-27 cells. In the presence of linopirdine, ACh failed to evoke a further inward current, but ACh still elicited a n outward current, thus suggesting that the Ca2+-dependent K+ current is rather insensitive to linopirdine. Linopirdine also inhibited anoth er voltage-gated potassium current (I-K(V)) at the concentration of 72 .3 mu M. Finally, the inhibitory effect of linopirdine on I-K(M), was confirmed in pyramidal neurons acutely dissociated from the rat cerebr al cortex at 35.8 mu M. The results suggest that Linopirdine is thus c onsidered to be an inhibitor of some type of K+ channels in both NGPM1 -27 cells and the rat cerebral neurons. (C) 1998 Elsevier Science B.V. All rights reserved.