Phrenic long-term facilitation requires 5-HT receptor activation during but not following episodic hypoxia

J Appl Physiol (1985). 2001 May;90(5):2001-6; discussion 2000. doi: 10.1152/jappl.2001.90.5.2001.


Episodic hypoxia evokes a sustained augmentation of respiratory motor output known as long-term facilitation (LTF). Phrenic LTF is prevented by pretreatment with the 5-hydroxytryptamine (5-HT) receptor antagonist ketanserin. We tested the hypothesis that 5-HT receptor activation is necessary for the induction but not maintenance of phrenic LTF. Peak integrated phrenic nerve activity (integralPhr) was monitored for 1 h after three 5-min episodes of isocapnic hypoxia (arterial PO(2) = 40 +/- 2 Torr; 5-min hyperoxic intervals) in four groups of anesthetized, vagotomized, paralyzed, and ventilated Sprague-Dawley rats [1) control (n = 11), 2) ketanserin pretreatment (2 mg/kg iv; n = 7), and ketanserin treatment 0 and 45 min after episodic hypoxia (n = 7 each)]. Ketanserin transiently decreased integralPhr, but it returned to baseline levels within 10 min. One hour after episodic hypoxia, integralPhr was significantly elevated from baseline in control and in the 0- and 45-min posthypoxia ketanserin groups. Conversely, ketanserin pretreatment abolished phrenic LTF. We conclude that 5-HT receptor activation is necessary to initiate (during hypoxia) but not maintain (following hypoxia) phrenic LTF.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Hypoxia / physiopathology*
  • Ketanserin / pharmacology
  • Male
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Phrenic Nerve / drug effects
  • Phrenic Nerve / physiology*
  • Phrenic Nerve / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / physiology*
  • Respiratory Mechanics / physiology*
  • Serotonin Antagonists / pharmacology


  • Receptors, Serotonin
  • Serotonin Antagonists
  • Ketanserin