ATP in the lateral hypothalamus/perifornical area enhances the CO2 chemoreflex control of breathing

Abstract

New Findings: What is the central question of this study? ATP is known to modulate the chemosensitivity of some brain areas. However, whether the ATP contributes specifically to the mechanism of chemoreception in the lateral hypothalamus/perifornical area (LH/PFA) remains to be determined. What is the main finding and its importance? ATP, acting on the LH/PFA, enhances the hypercapnic ventilatory response in rats during wakefulness, in the dark period. Our results highlight the importance of ATP as a modulator of central chemoreception and provide new insight regarding the mechanisms involved in LH/PFA chemosensitivity and the sleep–wake differences in the CO2/H+-dependent drive to breathe. Abstract: The lateral hypothalamus/perifornical area (LH/PFA) is a central chemoreceptor site, which acts in an arousal state-dependent manner. It has been shown that purinergic signalling through ATP influences the CO2/H+ responsiveness of other chemosensitive regions, but it is unknown whether ATP is also involved in the mechanisms that underlie LH/PFA chemoreception. Here, we studied the effects of microdialysis of a P2X-receptor agonist [α,β-methylene ATP (α,β-meATP), 10 mm] and a non-selective P2-receptor antagonist [pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonate (PPADS), 1 mm] into the LH/PFA of conscious rats on ventilation in room air and in 7% CO2. In the dark (active) phase, but not in the light, microdialysis of α,β-meATP caused an augmented hypercapnic ventilatory response during wakefulness, but not during non-REM sleep (P < 0.001). PPADS caused no change in CO2 ventilatory responses in either the dark period or the light period. Our data suggest that ATP in LH/PFA contributes to the hypercapnic ventilatory response in conscious rats during wakefulness in the dark phase of the diurnal cycle.