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This Article Full Text Full Text (PDF) All Versions of this Article: 586/8/2171    most recent jphysiol.2007.149047v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Mahamed, S. Articles by Mitchell, G. S. PubMed PubMed Citation Articles by Mahamed, S. Articles by Mitchell, G. S. Related Collections Respiratory

¹ Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706, USA

Long-term facilitation (LTF) is a form of respiratory neuroplasticity frequently induced by acute intermittent isocapnic hypoxia (AIH, three 5 min isocapnic hypoxic episodes). Although repetitive apnoeas are a frequent natural occurrence producing brief (< 30 s) episodes of hypoxia and hypercapnia, it is unknown if repetitive apnoeas also elicit LTF. Apnoea-induced LTF may preserve upper airway patency during sleep, thereby limiting further apnoeic events. We tested the hypothesis that repeated, brief ventilator-induced apnoeas are sufficient to induce serotonin-dependent phrenic and hypoglossal (XII) LTF in anaesthetized rats. Anaesthetized, male Sprague–Dawley rats were exposed to three or six 25 s ventilator apnoeas with 5 min intervals, and compared to time control and AIH-treated rats. Three and six ventilator apnoeas induced phrenic and XII LTF with a magnitude similar to AIH. Both apnoea-induced and AIH-induced LTF were associated with a decreased CO₂ recruitment threshold for phrenic and XII activity (4 mmHg). Spinal methysergide, a serotonin receptor antagonist, blocked apnoea-induced LTF but not changes in the CO₂-recruitment threshold. Thus, brief ventilator apnoeas elicit phrenic and XII LTF. Similar to AIH-induced LTF, apnoea-induced LTF is serotonin dependent, and the relevant serotonin receptors for phrenic LTF are located in the cervical spinal cord. Apnoea-induced LTF may have implications for the maintenance of breathing stability, particularly during sleep.

(Received 28 November 2007; accepted after revision 21 February 2008; first published online 21 February 2008)
Corresponding author G. S. Mitchell: Department of Comparative Biosciences, University of Wisconsin, 2015 Linden Drive, Madison, WI 3706-1102, USA. Email: mitchell{at}svm.vetmed.wisc.edu