Respiratory Network Stability and Modulatory Response to Substance P Require Nalcn

Szu Ying Yeh, Wei Hsiang Huang, Wei Wang, Christopher S. Ward, Eugene S. Chao, Zhenyu Wu, Bin Tang, Jianrong Tang, Jenny J. Sun, Meike Esther van der Heijden, Paul A. Gray, Mingshan Xue, Russell S. Ray, Dejian Ren, Huda Y. Zoghbi

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Respiration is a rhythmic activity as well as one that requires responsiveness to internal and external circumstances; both the rhythm and neuromodulatory responses of breathing are controlled by brainstem neurons in the preBötzinger complex (preBötC) and the retrotrapezoid nucleus (RTN), but the specific ion channels essential to these activities remain to be identified. Because deficiency of sodium leak channel, non-selective (Nalcn) causes lethal apnea in humans and mice, we investigated Nalcn function in these neuronal groups. We found that one-third of mice lacking Nalcn in excitatory preBötC neurons died soon after birth; surviving mice developed apneas in adulthood. Interestingly, in both preBötC and RTN neurons, the Nalcn current influences the resting membrane potential, contributes to maintenance of stable network activity, and mediates modulatory responses to the neuropeptide substance P. These findings reveal Nalcn's specific role in both rhythmic stability and responsiveness to neuropeptides within the respiratory network.

Original languageEnglish
Pages (from-to)294-303.e4
Issue number2
StatePublished - 19 Apr 2017
Externally publishedYes


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