Both linopirdine- and WAY123,398-sensitive components of I-K(M,I-ng) are modulated by cyclic ADP ribose in NG108-15 cells

The "M-like" current in NG108-15 cells has two components carried by differ ent K+ channels: a fast-deactivating component, analogous to I-K(M) in symp athetic neurones and carried by KCNQ2/3 channels, and a more slowly deactiv ating component carried by murine erg1 (merg1) channels. The former is sele ctively blocked by linopirdine (less than or equal to 10 muM), the latter b y WAY123,398 (less than or equal to 10 muM). Bradykinin (100 nM) inhibited 76% of the KCNQ component of current compared with 12% of the merg componen t. Cyclic ADP ribose (cADPR, 2 muM), introduced via the patch pipette, caus ed a rundown of both current components. Acetylcholine (100 muM) inhibited 89% of the KCNQ component of current compared to 34% of the merg component. After 15 min of intracellular dialysis with the cADPR antagonist 8-amino-c ADP ribose (100 muM), the inhibition reduced to 40% and 19% and after 30 mi n it was further reduced to 8% and 5% for the KCNQ currents and merg curren ts respectively. These data show that both KCNQ and merg currents in NG108- 15 cells can be modulated by either bradykinin or M-1 muscarinic receptors. The inhibition of the KCNQ current component is more pronounced than that of the merg component. These results suggest that cADPR might be involved i n M-1-muscarinic inhibition of both KCNQ2/3 and merg1 channels.