Respiratory disturbances and high risk of sudden death in the neonatal connexin ‐36 knockout mouse

Neonatal Cx36-knockout mice show breathing instability at rest, exacerbated chemoreflexes, disturbances in the mechanisms of cardiorespiratory coupling, and an elevated risk of sudden infant death. The principal determinants leading to the sudden infant death in the Cx36-knockout mice submitted to hypoxic-hypercapnic stress were the oxygen desaturation caused by the early suppression of mechanisms of cardiorespiratory coordination and the generation of a paroxysmal generalized clonic-tonic activity that changes of respiratory pattern from eupneic to a gasping mode. AbstractNeural circuits at the brainstem involved in the central generation of the motor patterns of respiration and cardiorespiratory chemoreflexes organize as cell assemblies connected by chemical and electrical synapses. However, the role played by the electrical connectivity mainly mediated by connexin36 (Cx36), which expression reaches peak value during the postnatal period, is still unknown. To address this issue, we analyzed here the respiratory phenotype of a mouse strain devoid constitutively of Cx36 at P14. Male Cx36-knockout mice at rest showed respiratory instability of variable degree, including a periodic Cheyne –Stokes breathing. Moreover, mice lacking Cx36 exhibited exacerbated chemoreflexes to normoxic and hypoxic hypercapnia characterized by a stronger inspiratory/expiratory coupling due to an increased sensitivity to CO2. Deletion of Cx36 also impaired the generation of the recurrent episodes o...
Source: Physiological Reports - Category: Physiology Authors: Tags: ORIGINAL ARTICLE Source Type: research