Abstract
At least four mechanisms have been proposed to elucidate how neurons in the retrotrapezoid (RTN) region sense changes in CO(2)/H(+) to regulate breathing (i.e., function as respiratory chemosensors). These mechanisms include: (1) intrinsic neuronal sensitivity to H(+) mediated by TASK-2 and GPR4; (2) paracrine activation of RTN neurons by CO(2)-responsive astrocytes (via a purinergic mechanism); (3) enhanced excitatory synaptic input or disinhibition; and (4) CO(2)-induced vascular contraction. Although blood flow can influence tissue CO(2)/H(+) levels, there is limited understanding of how control of vascular tone in central CO(2) chemosensitive regions might contribute to respiratory output. In this review, we focus on recent evidence that CO(2)/H(+)-induced purinergic-dependent vasoconstriction in the ventral parafacial region near RTN neurons supports respiratory chemoreception. This mechanism appears to be unique to the ventral parafacial region and opposite to other brain regions, including medullary chemosensor regions, where CO(2)/H(+) elicits vasodilatation. We speculate that this mechanism helps to maintain CO(2)/H(+) levels in the vicinity of RTN neurons, thereby maintaining the drive to breathe. Important next steps include determining whether disruption of CO(2)/H(+) vascular reactivity contributes to or can be targeted to improve breathing problems in disease states, such as Parkinson's disease.