Respiratory pattern and hypoxic ventilatory response in mice functionally lacking alpha2A-adrenergic receptors.

Abstract

In newborn mammals including man the respiratory pattern undergoes changes during the neonatal period10, 11, 26, 27, 36.These developmental changes are characterized by an increase in the duration of inspiratory time (TI), which in species born after relatively short gestations such as opossum10 and mouse27 can be quite marked. In addition to developmental differences in metabolism, pulmonary mechanics and stimulatory input from the periphery the intrinsic membrane properties of inspiratory neurons may contribute to this lengthening of TI. Spike frequency adaptation and afterhyperpolarization is present as early as postnatal day 1 (P1) in rat hypoglossal motoneurons35 and PO in mouse inspiratory neurons located in the pre-Bötzinger complex (PBC)28. Entry of calcium through high-voltage-activated (HVA) calcium channels has been shown to be essential for the generation of the AHP in PBC neurons9, ventral nucleus of the solitary tract29 and hypoglossal motoneurons32, 33 by activating slow-conductance calcium-activated potassium channels29,34. Therefore, the inhibiting modulation of HVA calcium channels during development is a potential mechanism by which TI could be prolonged. α2a adrenergic receptors which are coupled by pertussis toxin sensitive G proteins to various effectors, including inhibition of voltage activated Ca2+ channels20, and have been demonstrated in cardiorespiratory areas of the medulla1, 31 are candidates for this role. In order to evaluate their importance respiratory timing in the postnatal period was examined in mice who functionally lack α2a adrenergic receptors.KeywordsRespiratory FrequencyAcute HypoxiaRespiratory PatternLocus Coeruleus NeuronSpike Frequency AdaptationThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.