Received December 8, 2004
Revised February 3, 2005
Accepted after revision February 22, 2005

¹ University of Virginia

^* To whom correspondence should be addressed. E-mail: pgg{at}virginia.edu.

	Abstract

Central chemoreception is the mechanism by which arterial blood pCO2 is detected by the CNS to regulate breathing. Two main theories have been proposed to account for the phenomenon. The distributed chemosensitivity theory argues that pH-sensitivity is a widespread attribute of brainstem neurons and that central chemoreception results from the cumulative effects of pH on countless neurons. The specialized chemoreceptor theory envisions the existence of small and specialized populations of CNS cells (chemoreceptors) that are unique in their ability to detect very small pH fluctuations and, via specific connections, regulate a respiratory network that is itself unresponsive to pH. The recently identified CO2-sensitive neurons of the retrotrapezoid nucleus (RTN) seem to possess most of the attributes that one would expect of such chemoreceptors. This study also suggests that many fewer medullary neurons are intrinsically responsive to CO2 in vivo than might have been anticipated from prior experimentation in vitro. The properties of RTN neurons provide renewed support for the specialized chemoreceptor theory of central chemoreception, proposed in the early 1960s. However, many uncertainties remain, especially as regards the molecular mechanisms of chemoreception, the type of cell that actually detects pH in vivo (neuron, glia or others) and the number and location of bona fide central chemoreceptors.

Key Words: Brainstem, Chemoreceptor, Respiration

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