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Published on: November 19, 2015
Modulation of respiratory rhythmogenesis by chloride-mediated conductances during the perinatal period
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.
Abstract:
Respiratory rhythmogenesis is modulated by chloride-mediated conductances via GABAA and glycine receptors. In this study, we determine the actions of chloride-mediated conductances on respiratory rhythmogenesis in perinatal rats from the time of inception of fetal inspiratory drive through to the newborn period. Data were obtained from perinatal rat models, including (1) recordings of nerve roots and neuronal population discharge from medullary slice and brainstem-spinal cord in vitro preparations, (2) gramicidin perforated-patch recordings of respiratory neurons in medullary slices, and (3) plethysmographic recordings from unanesthetized pups. The transition from excitatory to inhibitory effects on respiratory rhythmogenesis occurs at approximately embryonic day 19. By birth, GABA, glycine, and taurine all induce a hyperpolarization of the membrane potential in respiratory medullary neurons and a suppression of respiratory frequency. The age-dependant change in the actions of chloride-mediated conductances is regulated by the development of chloride cotransporters (KCC2 and NKCC1). The function of KCC2 chloride cotransporter is strongly modulated by [K+]o, which must be considered when evaluating responses observed using in vitro perinatal preparations.
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