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Influence of 5‐HT2A receptor blockade on hypercapnic ventilatory response in arterially‐perfused adult rat
Author(s) -
Bale Tejus A,
Solomon Irene C
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.621.8
Subject(s) - hypercapnia , serotonergic , blockade , medicine , raphe , endocrinology , phrenic nerve , serotonin , perfusion , receptor , ketanserin , chemistry , anesthesia , respiratory system , neuroscience , 5 ht receptor , biology
A number of pathologies of breathing are postulated to arise from the failure to sense or respond appropriately to elevated levels of CO 2 (hypercapnia). Serotonergic raphe neurons have been identified as putative respiratory CO 2 chemosensors, and accumulating evidence suggests that disturbances in the serotonergic system may underlie these breathing pathologies. However, the role of serotonin (5‐HT) signaling in the hypercapnic ventilatory response has yet to be fully characterized. To begin to address this issue, we examined the effects of 5‐HT 2A receptor blockade on the phrenic nerve discharge response to elevated levels of CO 2 in 5 arterially‐perfused adult rat preparations. 5‐HT 2A receptors were blocked using ketanserin (KTN; 40 μM). Although perfusion with KTN increased the frequency and decreased the amplitude of basal phrenic bursts, increasing the CO 2 gassing the aCSF from 5‐10% further increased burst frequency by ~26%, produced a small (~7%) increase in burst amplitude, shifted the time‐to‐peak activity to ~20% earlier in the burst, and decreased inspiratory neural network complexity. Similar effects were observed under control conditions but the magnitude of the frequency response was slightly greater and mediated only by decreases in T E during KTN perfusion. These data suggest that activation of 5‐HT 2A receptors may participate in the hypercapnic ventilatory response. Supported by NS045321