Carotid body (CB) glomus cells respond to hypoxia by releasing neurotransmitters, such as ATP, which are believed to stimulate excitatory receptors on apposed nerve endings of the carotid sinus nerves as well as bind to autoreceptors on the glomus cell membrane to modulate response magnitude. The CB response to hypoxia is small at birth and increases during postnatal maturation in mammals. As ATP has been shown to inhibit the glomus cell response to hypoxia via an autoreceptor mechanism, we hypothesized that ATP-mediated inhibition may vary with age and play a role in postnatal development of the hypoxia response magnitude. The effects of ATP on CB glomus cell intracellular calcium ([Ca2+]i) responses to hypoxia were studied at two ages, P0-1 and P14-18. The inhibitory effect of ATP or a stable ATP analog on the glomus cell response to hypoxia was greater in newborn rats compared to the more mature age group. Use of selective P2Y receptor agonists and antagonists suggests that the inhibitory effect of ATP on the glomus cell [Ca2+]i response to hypoxia may be mediated by a P2Y12 receptor. Thus, developmental changes in ATP-mediated glomus cell inhibition may play a role in carotid chemoreceptor postnatal maturation.
Carotid body Glomus cells Hypoxia ATP Postnatal Development Maturation Purinergic receptor
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This study was supported by grants from National Institutes of Health (HL-05621 NIH RO1) and Arkansas Biosciences Institute (ABI).
Benot AR, Lopez-Barneo J (1990) Feedback inhibition of Ca2+ currents by dopamine in glomus cells of the carotid body. Eur J Neurosci 2:809–812PubMedCrossRefGoogle Scholar
Conde SV, Obeso A, Vicario I, Rigual R, Rocher A, Gonzalez C (2006) Caffeine inhibition of rat carotid body chemoreceptors is mediated by A2A and A2B adenosine receptors. J Neurochem 98:616–628PubMedCrossRefGoogle Scholar
Gauda EB, Northington FJ, Linden J, Rosin DL (2000) Differential expression of a(2a), A(1)-adenosine and D(2)-dopamine receptor genes in rat peripheral arterial chemoreceptors during postnatal development. Brain Res 872:1–10PubMedCrossRefGoogle Scholar
Kemp PJ (2005) Hemeoxygenase-2 as an O2 sensor in K+ channel-dependent chemotransduction. Biochem Biophys Res Commun 338:648–652PubMedCrossRefGoogle Scholar
Kim I, Yang DJ, Donnelly DF, Carroll JL (2009) Fluoresceinated peanut agglutinin (PNA) is a marker for live O(2) sensing glomus cells in rat carotid body. Adv Exp Med Biol 648:185–190PubMedCrossRefGoogle Scholar
Ortega-Saenz P, Pascual A, Gomez-Diaz R, Lopez-Barneo J (2006) Acute oxygen sensing in heme oxygenase-2 null mice. J Gen Physiol 128:405–411PubMedCrossRefGoogle Scholar
Tomares SM, Bamford OS, Sterni LM, Fitzgerald RS, Carroll JL (1994) Effects of domperidone on neonatal and adult carotid chemoreceptors in the cat. J Appl Physiol 77:1274–1280PubMedGoogle Scholar
Wasicko MJ, Sterni LM, Bamford OS, Montrose MH, Carroll JL (1999) Resetting and postnatal maturation of oxygen chemosensitivity in rat carotid chemoreceptor cells. J Physiol 514(Pt 2):493–503PubMedCrossRefGoogle Scholar
Wasicko MJ, Breitwieser GE, Kim I, Carroll JL (2006) Postnatal development of carotid body glomus cell response to hypoxia. Respir Physiol Neurobiol 154:356–371PubMedCrossRefGoogle Scholar
Wyatt CN, Buckler KJ (2004) The effect of mitochondrial inhibitors on membrane currents in isolated neonatal rat carotid body type I cells. J Physiol 556:175–191PubMedCrossRefGoogle Scholar
Wyatt CN, Evans AM (2007) AMP-activated protein kinase and chemotransduction in the carotid body. Respir Physiol Neurobiol 157:22–29PubMedCrossRefGoogle Scholar
Xu J, Xu F, Tse FW, Tse A (2005) ATP inhibits the hypoxia response in type I cells of rat carotid bodies. J Neurochem 92:1419–1430PubMedCrossRefGoogle Scholar