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

Abstract

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 (∫Phr) 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 ∫Phr, but it returned to baseline levels within 10 min. One hour after episodic hypoxia, ∫Phr 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.