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Simulated apnoeas induce serotonin‐dependent respiratory long‐term facilitation in rats
Author(s) -
Mahamed Safraaz,
Mitchell Gordon S.
Publication year - 2008
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2007.149047
Subject(s) - anesthesia , serotonin , methysergide , medicine , respiratory system , phrenic nerve , intermittent hypoxia , hypoxia (environmental) , antagonist , control of respiration , ventilation (architecture) , hypercapnia , receptor , chemistry , oxygen , obstructive sleep apnea , organic chemistry , mechanical engineering , engineering
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 CO 2 recruitment threshold for phrenic and XII activity (∼4 mmHg). Spinal methysergide, a serotonin receptor antagonist, blocked apnoea‐induced LTF but not changes in the CO 2 ‐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.