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

Abstract

The "M-like" current in NG108-15 cells has two components carried by different K+ channels: a fast-deactivating component, analogous to IK(M) in sympathetic neurones and carried by KCNQ2/3 channels, and a more slowly deactivating component carried by murine erg1 (merg1) channels. The former is selectively blocked by linopirdine (< or =10 microM), the latter by WAY123,398 (< or =10 microM). Bradykinin (100 nM) inhibited 76% of the KCNQ component of current compared with 12% of the merg component. Cyclic ADP ribose (cADPR, 2 microM), introduced via the patch pipette, caused a rundown of both current components. Acetylcholine (100 microM) 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-cADP ribose (100 microM), the inhibition reduced to 40% and 19% and after 30 min it was further reduced to 8% and 5% for the KCNQ currents and merg currents respectively. These data show that both KCNQ and merg currents in NG108-15 cells can be modulated by either bradykinin or M1 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 in M1-muscarinic inhibition of both KCNQ2/3 and merg1 channels.