Calcium-activated ion channels drive atypical inhibition in medial habenula neurons.

ABSTRACT: Nicotine is an addictive substance that poses substantial health and societal challenges. Despite the known links between the medial habenula (MHb) and nicotine avoidance, the ionic mechanisms underlying MHb neuronal responses to nicotine remain unclear. Here, we report that MHb neurons use a long-lasting refractory period (LLRP) as an unconventional inhibitory mechanism to curb hyperexcitability. This process is initiated by nicotine-induced calcium influx through nicotinic acetylcholine receptors, which activates a calcium-activated chloride channel (CaCC). Owing to high intracellular chloride levels in MHb neurons, chloride efflux through CaCC, coupled with high-threshold voltage-gated calcium channels, sustains MHb depolarization near the chloride equilibrium potential of -30 millivolt

SUBMITTER: Kawai T 

PROVIDER: S-EPMC11922023 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature