Nitric oxide activates hypoglossal motoneurons by cGMP‐dependent inhibition of TASK channels and cGMP‐independent activation of HCN channels

Abstract

Nitric oxide (NO) is an important signaling molecule; however mechanism(s) underlying NO modulation of motoneurons (MNs) remain obscure. Here, we used a combination of in vivo and in vitro recording techniques to examine NO modulation of MNs in the hypoglossal motor nucleus (HMN). Microperfusion of DEA (NO donor) into the HMN of anesthetized adult rats increased genioglossus muscle activity. In the brain slice, whole‐cell current‐clamp recordings from hypoglossal MNs show that exposure to DEA depolarized membrane potential and increased responsiveness to depolarizing current injections. Under voltage‐clamp conditions, we found that NO inhibited a Ba2+‐sensitive background K+ conductance and activated a Cs+‐sensitive hyperpolarization‐activated inward current (Ih). The NO‐sensitive K+ conductance exhibited properties similar to TWIK‐related acid‐sensitive K+ (TASK) channels and was blocked by ODQ (soluble guanylyl cyclase antagonist) and KT5823 (PKG antagonist). In Ba2+, NO activated both the instantaneous (Iinst) and time‐dependent (Iss) components of Ih. Interestingly, at more hyperpolarized potentials NO preferentially increased Iinst, and this was retained in ODQ but blocked by a cysteine‐specific oxidant. These results suggest that NO activates hypoglossal MNs by cGMP‐dependent inhibition of a TASK‐like current and S‐nitrosylation‐ dependent activation of Ih.