| First Author | da Silva CA Jr | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 8 | Pages | 113000 |
| PubMed ID | 37590134 | Mgi Jnum | J:339953 |
| Mgi Id | MGI:7525064 | Doi | 10.1016/j.celrep.2023.113000 |
| Citation | da Silva CA Jr, et al. (2023) Role of Na(V)1.6-mediated persistent sodium current and bursting-pacemaker properties in breathing rhythm generation. Cell Rep 42(8):113000 |
| abstractText | Inspiration is the inexorable active phase of breathing. The brainstem pre-Botzinger complex (preBotC) 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 preBotC interneurons is essential for rhythmogenesis. We tested the pacemaker hypothesis by conditionally knocking out and knocking down the Scn8a (Na(v)1.6 [voltage-gated sodium channel 1.6]) gene in core rhythmogenic preBotC 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 of ventilation. Diminishing Scn8a via genetic interference has no impact on breathing in adult mice. We argue that the Scn8a-mediated I(NaP) is not obligatory but that it influences the development and rhythmic function of the preBotC. The ubiquity of the I(NaP) in respiratory brainstem interneurons could underlie breathing-related behaviors such as neonatal phonation or rhythmogenesis in different physiological conditions. |
