Influence of 5‐HT2A receptor blockade on hypercapnic ventilatory response in arterially‐perfused adult rat

Abstract

A number of pathologies of breathing are postulated to arise from the failure to sense or respond appropriately to elevated levels of CO2 (hypercapnia). Serotonergic raphe neurons have been identified as putative respiratory CO2 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‐HT2A receptor blockade on the phrenic nerve discharge response to elevated levels of CO2 in 5 arterially‐perfused adult rat preparations. 5‐HT2A 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 CO2 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 TE during KTN perfusion. These data suggest that activation of 5‐HT2A receptors may participate in the hypercapnic ventilatory response. Supported by NS045321