Astrocyte chemoreceptors: mechanisms of H+ sensing by astrocytes in the retrotrapezoid nucleus and their possible contribution to respiratory drive

Central chemoreception is the mechanism by which CO2/pH-sensitive neurons (i.e. chemoreceptors) regulate breathing, presumably in response to changes in tissue pH. A region of the brainstem called the retrotrapezoid nucleus (RTN) is thought to be an important site of chemoreception; select neurons (i.e. chemoreceptors) in this region sense changes in CO2/H+ and send excitatory glutamatergic drive to respiratory centres to modulate the depth and frequency of breathing. Purinergic signalling may also contribute to chemoreception; for instance, it was shown in vivo that CO2/H+ facilitates ATP release within the RTN to stimulate breathing, and recent evidence suggests that CO2/H+-sensitive RTN astrocytes are the source of this purinergic drive to breathe. In this review, we summarize evidence that RTN astrocytes sense changes in CO2/H+, identify mechanisms that are likely to confer CO2/H+ sensitivity to RTN astrocytes, including inhibition of heteromeric Kir4.1-Kir5.1 channels and activation of a depolarizing inward current generated by the sodium bicarbonate cotransporter, and discuss the extent to which astrocytes contribute to respiratory drive.