Regulation of ventral surface CO2/H+-sensitive neurons by purinergic signalling

Author(s)

Wenker, Ian C. ^[1] ; Sobrinho, Cleyton R. ^[2] ; Takakura, Ana C. ^[3] ; Moreira, Thiago S. ^[2] ; Mulkey, Daniel K. ^[1]

Affiliation

^[1] Univ Connecticut, Dept Physiol & Neurobiol, Storrs, CT 06269 - USA

^[2] Univ Sao Paulo, Dept Pharmacol, BR-05508 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Dept Physiol & Biophys, BR-05508 Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF PHYSIOLOGY-LONDON; v. 590, n. 9, p. 2137-2150, MAY 2012.
• Web of Science Citations: 51

Abstract

Central chemoreception is the mechanism by which the brain regulates breathing in response to changes in tissue CO2/H+. Abrainstemregion called the retrotrapezoid nucleus (RTN) contains a population of CO2/H+-sensitive neurons that appears to function as an important chemoreceptor. Evidence also indicates that CO2-evoked ATP release from RTN astrocytes modulates activity of CO2/H+-sensitive neurons; however, the extent to which purinergic signalling contributes to chemoreception by RTN neurons is not clear and the mechanism(s) underlying CO2/H+-evoked ATP release is not fully elucidated. The goals of this study are to determine the extent to which ATP contributes to RTN chemoreception both in vivo and in vitro, andwhether purinergic drive to chemoreceptors relies on extracellularCa(2+) or gap junction hemichannels. We also examine the possible contribution of P2Y1 receptors expressed in theRTNto the purinergic drive to breathe. We showthat purinergic signalling contributes, in part, to the CO2/H+ sensitivity of RTN neurons. In vivo, phrenic nerve recordings of respiratory activity in adult rats show that bilateral injections of pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate (PPADS, a P2 receptor blocker) decreased the ventilatory response to CO2 by 30%. In vitro, loose-patch recordings from RTN neurons show that P2 receptor blockers decreased responsiveness to both 10% and 15% CO2 also by 30%. In the slice, the contribution of purinergic signalling to RTN chemoreception did not increase with temperature (22-35 degrees C) and was retained in low extracellular Ca2+ medium. Conversely, the gap junction blockers carbenoxolone and cobalt decreased neuronal CO2/H+ sensitivity by an amount similar to P2 receptor antagonists. Inhibition of the P2Y1 receptor in the RTN had no effect on CO2 responsivness in vitro or in vivo; thus, the identity of P2 receptors underlying the purinergic component of RTN chemoreception remains unknown. These results support the possibility that CO2/H+-evoked ATP release is mediated by a mechanism involving gap junction hemichannels. (AU)

• FAPESP's process: 11/13462-7 - The interaction between retrotrapezoid nucleus astrocytes and neurons on respiratory responses promoted by central chemoreflex activation
• Grantee: Cleyton Roberto Sobrinho
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/09776-3 - Neural mechanisms involved in expiratory rhythm generator: possible involvement of the retrotrapezoid nucleus and the parafacial region
• Grantee: Ana Carolina Thomaz Takakura
• Support type: Research Grants - Young Investigators Grants
• FAPESP's process: 10/19336-0 - Pontine mechanisms involved in cardiorespiratory control during central or peripheral chemoreceptors activation
• Grantee: Thiago dos Santos Moreira
• Support type: Regular Research Grants