Sodium Leak Channel in Glutamatergic Neurons of the Lateral Parabrachial Nucleus Helps to Maintain Respiratory Frequency Under Sevoflurane Anesthesia

Neurosci Bull. 2024 Aug;40(8):1127-1140. doi: 10.1007/s12264-024-01223-0. Epub 2024 May 20.

Abstract

The lateral parabrachial nucleus (PBL) is implicated in the regulation of respiratory activity. Sodium leak channel (NALCN) mutations disrupt the respiratory rhythm and influence anesthetic sensitivity in both rodents and humans. Here, we investigated whether the NALCN in PBL glutamatergic neurons maintains respiratory function under general anesthesia. Our results showed that chemogenetic activation of PBL glutamatergic neurons increased the respiratory frequency (RF) in mice; whereas chemogenetic inhibition suppressed RF. NALCN knockdown in PBL glutamatergic neurons but not GABAergic neurons significantly reduced RF under physiological conditions and caused more respiratory suppression under sevoflurane anesthesia. NALCN knockdown in PBL glutamatergic neurons did not further exacerbate the respiratory suppression induced by propofol or morphine. Under sevoflurane anesthesia, painful stimuli rapidly increased the RF, which was not affected by NALCN knockdown in PBL glutamatergic neurons. This study suggested that the NALCN is a key ion channel in PBL glutamatergic neurons that maintains respiratory frequency under volatile anesthetic sevoflurane but not intravenous anesthetic propofol.

Keywords: General anesthesia; Glutamatergic neurons; Lateral parabrachial nucleus; NALCN; Respiration.

MeSH terms

  • Anesthetics, Inhalation* / pharmacology
  • Animals
  • Glutamic Acid / metabolism
  • Ion Channels
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Neurons* / drug effects
  • Neurons* / metabolism
  • Parabrachial Nucleus* / drug effects
  • Propofol / pharmacology
  • Respiration / drug effects
  • Respiratory Rate / drug effects
  • Sevoflurane* / pharmacology
  • Sodium Channels / drug effects
  • Sodium Channels / metabolism

Substances

  • Sevoflurane
  • Anesthetics, Inhalation
  • NALCN protein, mouse
  • Sodium Channels
  • Propofol
  • Glutamic Acid
  • Ion Channels
  • Membrane Proteins