The KCNQ channel inhibitor XE991 suppresses nicotinic acetylcholine receptor-mediated responses in rat intracardiac ganglion neurons

Background XE991 (10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone) is reportedly a potent and selective Kv7 (KCNQ) channel inhibitor. This study aimed to evaluate how XE991 affects nicotinic responses in intracardiac ganglion neurons. Methods We studied how the KCNQ channel inhibitor XE991 could affect nicotinic responses in acutely isolated rat intracardiac ganglion neurons using a perforated patch-clamp recording configuration and Ca2+ imaging. Results XE991 reversibly and concentration-dependently inhibited the nicotine (10 mu M)-induced current with an IC50 of 14.4 mu M. The EC50 values for nicotine-induced currents in the absence and presence of 10 mu M XE991 were 8.7 and 12.0 mu M, respectively. Because XE991 suppressed the maximum response of the nicotine concentration-response curve, the inhibitory effect of this drug appears to be noncompetitive. In addition, linopirdine reduced the amplitude of 10 mu M nicotine-induced currents with an IC50 value of 16.9 mu M. The inorganic KCNQ channel inhibitor Ba2+ affected neither the nicotine-induced current nor the inhibitory effect of XE991 on the nicotinic response. The KCNQ activator flupirtine at a concentration of 10 mu M slightly but markedly inhibited the nicotine-induced current. Finally, XE991 inhibited the nicotine-induced elevation of intracellular calcium concentration and the nicotine-induced firing of action potentials. Conclusion We propose that XE991 inhibits nicotinic acetylcholine receptors in intracardiac ganglion neurons, which in turn attenuate nicotine-induced neuronal excitation.

Automated summary

In this study, it was found that XE991, a potent and selective Kv7 (KCNQ) channel inhibitor, can inhibit nicotinic responses in intracardiac ganglion neurons. This drug reduces nicotine-induced neuronal excitation by suppressing the nicotine-induced current and intracellular calcium concentration elevation.