ATP and astrocytes are involved in the lamprey respiratory control

ATP and astrocytes are involved in the lamprey respiratory control. Ludovica Iovino, E. Cinelli, D. Mutolo, F. Bongianni. Dipartimento di Medicina Sperimentale e Clinica, Sezione Scienze Fisiologiche, Università degli Studi di Firenze, Viale G.B. Morgagni 63, 50134 Firenze, Italy The paratrigeminal respiratory group (pTRG) is a brainstem region responsible for the respiratory rhythm generation in the lamprey, a lower vertebrate that has proved to be highly useful to demonstrate that the basic features of rhythmogenic networks have been conserved throughout vertebrate evolution. It is well known that ATP is involved in the control of respiration and that astrocytes contribute to the purinergic modulation. Since no information is available on the role of ATP and astrocytes within the lamprey respiratory network, experiments were performed on isolated brainstems of lampreys. The vagal motor output was used to monitor respiratory activity. Bilateral microinjections (30-50 nl) of 1 mM ATP into the pTRG caused marked increases in respiratory frequency followed by decreases in respiratory motor output due to the ATP metabolite adenosine. Increases in respiratory frequency were mimicked by similar microinjections of 1 mM ATP-γ-S, a nonhydrolyzable ATP agonist, while decreases were induced by microinjections of 0.5 mM adenosine. Bath applications and microinjections of selective agonists and antagonists of purinergic receptors showed that ATP increased respiratory activity by acting on pTRG P2X receptors. To disclose the respiratory role of astrocytes, bath application of the gliotoxin aminoadipic acid (1 mM) was employed. This manouvre dramatically depressed the respiratory motor output. Interestingly, under these conditions, the responses to ATP-γ-S microinjected into the pTRG were abolished, indicating that pTRG astrocytes play a key respiratory role. Consistently with the glial function of providing glutamine to neurons for glutamate synthesis, bath application of 5 mM glutamine caused a rapid recovery of baseline respiration. The results show for the first time that ATP and astrocytes strongly contribute to the modulation of the lamprey respiratory pattern. Their function in rhythmic networks appears to be phylogenetically conserved.