A debate has raged since the discovery of central and peripheral respiratory chemoreceptors as to whether the reflexes they mediate combine in an additive (i.e., no interaction), hypoadditive or hyperadditive manner. Here we critically review pertinent literature related to O2 and CO2 sensing from the perspective of system integration and summarize many of the studies on which these seemingly opposing views are based. Despite the intensity and quality of this debate, we have yet to reach consensus, either within or between species. In reviewing this literature, we are struck by the merits of the approaches and preparations that have been brought to bear on this question. This suggests that either the nature of combination is not important to system responses, contrary to what has long been supposed, or that the nature of the combination is more malleable than previously assumed, changing depending on physiological state and/or respiratory requirement.
Copyright © 2016 John Wiley & Sons, Inc.