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-1 adrenergic receptors and serotonin 5HT2 receptors
1 Physiology, Dartmouth Medical School, Lebanon, New Hampshire, United States
2 Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire, United States
* To whom correspondence should be addressed. E-mail: walter.m.stjohn{at}dartmouth.edu.
In severe hypoxia or ischaemia, normal eupneic breathing fails and is replaced by gasping. Gasping serves as part of a process of autoresuscitation by which eupnea is re-established. Medullary neurons, having a burster, pacemaker discharge, underlie gasping. Conductance through persistent sodium channels is essential for the burster discharge. This conductance is modulated by norepinephrine, acting on 
-1 adrenergic receptors, and serotonin, acting on 5HT2 receptors. We hypothesized that blockers of 5HT2 receptors and -1 adrenergic receptors would alter autoresuscitation. The in situ perfused preparation of the juvenile rat was used. Integrated phrenic discharge was switched from an incrementing pattern, akin to eupnea, to the decrementing pattern comparable to gasping in hypoxic hypercapnia. With a restoration of hyperoxic normocapnia, rhythmic, incrementing phrenic discharge returned within 10 s in most preparations. Following addition of blockers of 1 adrenergic receptors (WB 4101, 0.0625 to 0.500µM) and/or blockers of 5-HT2 (ketanserin, 1.25 to 10 µM) or multiple 5-HT receptors (methysergide, 3.0 to 10 µM) to the perfusate, incrementing phrenic discharge continued. Fictive gasping was still induced, although it ceased after significantly fewer decrementing bursts than in preparations than received no blockers. Moreover, the time for recovery of rhythmic activity was significantly prolonged. This prolongation was in excess of 100 s in all preparations that received both WB 4101 (above 0.125 µM) and methysergide (above 2.5 µM). We conclude that activation of -1 adrenergic and 5-HT2 receptors is important to sustain gasping and to restore rhythmic respiratory activity after hypoxia-induced depression.
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