Interactions between purinergic receptors and Kir channels in neurovascular coupling

We previously noted a large overlap in the contributions from adenosine (ADO) and K + ‐ channels in the process of neurovascular coupling (NVC), implying the presence of interactive mechanisms. In this study, we assessed whether neural activation‐related pial arteriolar dilation (PAD) involved interactions among A 2A receptors, large‐conductance Ca 2+ ‐operated K + (BK Ca ) channels, and inward rectifier K + channels (K ir ). In rats with closed cranial windows, we monitored sciatic nerve stimulation (SNS)‐induced PAD in the absence or presence of an A 2A blocker (ZM 241385, 10 μM), BK Ca blocker (paxilline [PAX], 10 μM), and K ir blocker (BaCl 2 , 100 μM). Each of these interventions led to a substantial (60–67%) suppression of SNS‐induced PADs, confirming the involvement of A 2A receptors and BK Ca and K ir channels in NVC. Furthermore, cortical suffusion of ADO, NS1619 and KCl evoked dose‐dependent PADs, which were subsequent blunted (by 56–70%) in the presence of 100 μM BaCl 2 . On the other hand, the presence of PAX abolished NS1619‐induced PAD, without affecting ADO or KCl‐related PAD. Results suggest that enhancing K ir function via the increased activities of both A 2A and BK pathways represents an important mechanism of NVC. We speculate that the K ir ‐dependence of the ADO response may involve A 2A ‐mediated cAMP generation and subsequent phosphorylation‐related potentiation of K ir channel function.