Modulation of respiratory rhythmogenesis by chloride-mediated conductances during the perinatal period

Jun Ren1, John J Greer

  • 1Department of Physiology, Centre for Neuroscience, University of Alberta, Edmonton, Alberta, T6G 2S2, Canada.

Insights

Chloride conductances shift from exciting to inhibiting respiratory rhythm in developing rats around embryonic day 19, impacting breathing frequency and neuron membrane potential via chloride cotransporters.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Respiratory Physiology

Background:

  • Respiratory rhythmogenesis relies on chloride-mediated conductances acting through GABAA and glycine receptors.
  • Understanding the developmental trajectory of these conductances is crucial for perinatal respiratory control.

Purpose of the Study:

  • To investigate the developmental changes in chloride-mediated conductances influencing respiratory rhythmogenesis in perinatal rats.
  • To identify the specific developmental period when the functional role of these conductances transitions.

Main Methods:

  • Utilized in vitro medullary slice and brainstem-spinal cord preparations from perinatal rats.
  • Performed gramicidin perforated-patch recordings on medullary respiratory neurons.
  • Conducted plethysmographic recordings in unanesthetized rat pups.

Main Results:

  • A developmental transition from excitatory to inhibitory effects of chloride-mediated conductances on respiratory rhythmogenesis was observed around embryonic day 19.
  • By birth, GABA, glycine, and taurine induced hyperpolarization and suppressed respiratory frequency in medullary neurons.
  • The developmental shift is linked to the maturation of chloride cotransporters, specifically KCC2 and NKCC1.

Conclusions:

  • Chloride-mediated conductances play a dynamic role in perinatal respiratory rhythmogenesis, with a critical transition occurring near birth.
  • The expression and function of chloride cotransporters (KCC2, NKCC1) are key regulators of this developmental change.
  • Extracellular potassium ([K+]o) influences KCC2 function, a factor to consider in in vitro perinatal preparations.

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