title: Respiratory Network Stability and Modulatory Response to Substance P Require Nalcn.
abstract: 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.
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Szu-Ying
authors.initials: SY
authors.lastname: Yeh
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Wei-Hsiang
authors.initials: WH
authors.lastname: Huang
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Ward
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA; The Cain Foundation Laboratories at Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: Eugene S
authors.initials: ES
authors.lastname: Chao
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Jenny J
authors.initials: JJ
authors.lastname: Sun
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Meike
authors.initials: M
authors.lastname: Esther van der Heijden
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gray
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA; The Cain Foundation Laboratories at Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: Mingshan
authors.initials: M
authors.lastname: Xue
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Russell S
authors.initials: RS
authors.lastname: Ray
authors.affiliation: Department of Biology, University of Pennsylvania, 415 South University Avenue, Philadelphia, PA 19104, USA.
authors.forename: Dejian
authors.initials: D
authors.lastname: Ren
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: hzoghbi@bcm.edu.
authors.forename: Huda Y
authors.initials: HY
authors.lastname: Zoghbi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D010507:Periodicity; D012125:Respiratory Center / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*
chemical_list: D015222:Sodium Channels; D013373:Substance P; D012964:Sodium; D002118:Calcium