Patrice G. Guyenet , Douglas A. Bayliss, Daniel K. Mulkey, Ruth L. Stornetta, Thiago S. Moreira, Ana T. Takakura
Department of Pharmacology, University of Virginia, Charlottesville, USA
Abstract
The functional role of retrotrapezoid nucleus (RTN) neurons as the central chemoreceptors and the potential implications of Phox2b expressed in these neurons will be discussed. RTN resides at the ventral medullary surface. RTN lesions reduce central respiratory chemoreception (CRC). RTN neurons are glutamatergic propriobulbar interneurons that selectively innervate the ventral respiratory column and other medullary regions essential to breathing. Their response to CO2 is presumably intrinsic. RTN neurons uniformly express Phox2b, a transcription factor whose mutation in man causes a loss of CRC and central sleep apnea. RTN neurons are activated by stimulation of the carotid bodies, restrained by inhibitory inputs from the central respiratory pattern generator and from lung afferents and their response to CO2 is sensitized by serotonin and by peptides released by serotonin neurons. The properties of RTN neurons are consistent with those expected from specialized central respiratory chemoreceptors. These data also suggest that respiratory reflexes operate in part by regulating the activity of central chemoreceptors. RTN neurons and the neurons that relay carotid body inputs to the respiratory centers express Phox2b. This peculiarity probably accounts for the loss of CRC associated with Phox2b mutations in man (central congenital hypoventilation syndrome).
Keywords
Central chemoreception; Congenital hypoventilation syndrome; Retrotrapezoid nucleus; Transcription factor
