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Respiratory rhythm generation during gasping depends on persistent sodium current


In severe hypoxia, homeostatic mechanisms maintain function of the brainstem respiratory network. We hypothesized that hypoxia involves a transition from neuronal mechanisms of normal breathing (eupnea) to a rudimentary pattern of inspiratory movements (gasping). We provide evidence for hypoxia-driven transformation within the central respiratory oscillator, in which gasping relies on persistent sodium current, whereas eupnea does not depend on this cellular mechanism.

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Figure 1: Patterns of motor nerve and single-neuron activities during the eupneic pattern and gasping induced by hypoxic hypercapnia (5% O2, 8% CO2, 87% N2) in the in situ preparation from a juvenile (6-week-old) rat.
Figure 2: Respiratory activity in preBötzinger complex during eupnea and gasping.
Figure 3: Elimination of gasping by persistent sodium current blockers.


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We thank I. Rybak for comments on the manuscript. We are grateful for the financial support of the British Heart Foundation (to A.L.P.A. and J.F.R.P.) and the US National Institutes of Health (W.M.S.-J.). This research was also supported, in part, by the Intramural Research Program of the National Institute of Health, National Institute of Neurological Disorders and Stroke.

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Correspondence to Julian F R Paton.

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Supplementary information

Supplementary Fig. 1

Major fast excitatory and inhibitory synaptic transmission was blocked effectively by a cocktail of kynurenic acid, strychnine and bicuculline in the in situ preparation. (PDF 158 kb)

Supplementary Fig. 2

Pharmacological profile of block of persistent sodium current (NaP) by riluzole in neonatal rat pre-Bötzinger complex neurons in slices in vitro. (PDF 165 kb)

Supplementary Fig. 3

Transformation of respiratory motor pattern after pontine-medullary transection. a, control eupneic activity generated by the in situ preparation with pons intact. (PDF 150 kb)

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Paton, J., Abdala, A., Koizumi, H. et al. Respiratory rhythm generation during gasping depends on persistent sodium current. Nat Neurosci 9, 311–313 (2006).

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