Article Figures & Data
Figures
- Fig. 1.
Representative phrenic neurogram taken before, during, and 1 hr after intermittent hypoxia in rats pretreated with artificial CSF (A), methysergide (B; 250 μg/kg), or emetine (C; 1 μg/kg). In all rats, the integrated phrenic amplitude returned close to baseline levels immediately after intermittent hypoxia. Only rats pretreated with artificial CSF had a subsequent progressive increase in phrenic amplitude over the course of the next hour, indicating phrenic long-term facilitation.
- Fig. 2.
Spinal serotonin receptors are required for phrenic long-term facilitation. The mean percentage change in integrated phrenic (Phr; A) and hypoglossal (XII; B) discharge from baseline at 15, 30, and 60 min after intermittent hypoxia is shown. Intermittent hypoxia elicits phrenic and hypoglossal long-term facilitation in rats pretreated with intrathecal artificial CSF (●). Intrathecal methysergide (○; 250 μg/kg) abolished phrenic but not hypoglossal long-term facilitation. *Significantly increased from baseline (p < 0.05).#Significantly different from artificial CSF controls (p < 0.05).
- Fig. 3.
Spinal serotonin receptor activation is required for burst frequency long-term facilitation. The change in burst frequency from baseline 15, 30, and 60 min after intermittent hypoxia is shown. Intermittent hypoxia elicits long-term facilitation of burst frequency in rats intrathecally injected with artificial CSF (●) but not in rats intrathecally injected with methysergide (○; 250 μg/kg). #Significantly different from artificial CSF controls (p < 0.05). *Significantly increased from baseline (p < 0.05).
- Fig. 4.
Spinal protein synthesis is required for phrenic long-term facilitation. The mean percentage change in integrated phrenic (Phr; A) and hypoglossal (XII; B) discharge from baseline at 15, 30, and 60 min after intermittent hypoxia is shown in rats intrathecally injected with emetine (1 or 20–250 μg/kg), cycloheximide (250 μg/kg), or artificial CSF. Intermittent hypoxia elicits phrenic and hypoglossal long-term facilitation in rats injected with intrathecal artificial CSF (●). Intrathecal emetine (■; 1 μg/kg) and cycloheximide (○; 250 μg/kg) abolished phrenic, but not hypoglossal long-term facilitation. Rats pretreated with high doses of emetine (▪; 20–250 μg/kg) had no significant phrenic or hypoglossal long-term facilitation. *Significantly increased from baseline (p < 0.05).#Significantly different from artificial CSF controls (p < 0.05).
- Fig. 5.
Spinal protein synthesis is not required for burst frequency long-term facilitation. The change in burst frequency 15, 30, and 60 min after intermittent hypoxia is shown. Intermittent hypoxia elicits burst frequency long-term facilitation in rats intrathecally injected with artificial CSF (●), emetine (■; 1 μg/kg), or cycloheximide (○; 250 μg/kg). High doses of emetine that were likely not restricted to the spinal cord (▪; 20–250 μg/kg) blocked burst frequency LTF (p > 0.05). *Significantly increased from baseline (p < 0.05).
- Fig. 6.
Proposed mechanism of phrenic long-term facilitation. Intermittent hypoxia increases the release of serotonin in the vicinity of the synapse between descending bulbospinal respiratory neurons and phrenic dendrites. The activation of 5-HT2A receptors initiates a signal transduction cascade that leads to new protein synthesis. These newly synthesized proteins may act both presynaptically and postsynaptically to increase synaptic efficacy between bulbospinal respiratory neurons and phrenic motoneurons and hence may give rise to a facilitated phrenic motor output.
Tables
- Table 1.
Hypoxic ventilatory responses in rats pretreated with artificial CSF, methysergide, emetine (1 μg/kg), or cycloheximide
Amplitude change in hypoxia (% above baseline) Burst frequency (bursts/min) ∫Phr ∫XII Baseline Hypoxia Artificial CSF 111 ± 161-a 137 ± 281-a 36.2 ± 1.3 44.5 ± 1.31-a Methysergide 88 ± 101-a 119 ± 181-a 44.3 ± 1.61-b 48 ± 2 Emetine 172 ± 491-a 155 ± 141-a 40.2 ± 1.7 45.8 ± 1.81-a Cycloheximide 89 ± 131-a 199 ± 451-a 40.7 ± 2.4 49.4 ± 2.71-a All rat groups significantly increased integrated phrenic (∫Phr) and hypoglossal (∫XII) amplitude (percentage above baseline) similarly during hypoxia (p > 0.05). Rats pretreated with artificial CSF, emetine, or cycloheximide had a significant increase in burst frequency in hypoxia (p < 0.05). Rats pretreated with methysergide had a significantly elevated baseline frequency (p < 0.05) but did not have a significant increase in burst frequency during hypoxia (p > 0.05).
↵F1-a Significantly different from baseline.
↵F1-b Significantly different from artificial CSF control.
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