Role of Na_V1.6-mediated persistent sodium current and bursting-pacemaker properties in breathing rhythm generation.

ABSTRACT: Inspiration is the inexorable active phase of breathing. The brainstem pre-Bötzinger complex (preBötC) gives rise to inspiratory neural rhythm, but its underlying cellular and ionic bases remain unclear. The long-standing "pacemaker hypothesis" posits that the persistent Na⁺ current (I_NaP) that gives rise to bursting-pacemaker properties in preBötC interneurons is essential for rhythmogenesis. We tested the pacemaker hypothesis by conditionally knocking out and knocking down the Scn8a (Na_v1.6 [voltage-gated sodium channel 1.6]) gene in core rhythmogenic preBötC neurons. Deleting Scn8a substantially decreases the I_NaP and abolishes bursting-pacemaker activity, which slows inspiratory rhythm in vitro and negatively impacts the postnatal development

SUBMITTER: da Silva CA 

PROVIDER: S-EPMC10528911 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature