Interactions between purinergic receptors and Kir channels in neurovascular coupling

Abstract

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 A2A receptors, large‐conductance Ca2+‐operated K+ (BKCa) channels, and inward rectifier K+ channels (Kir). In rats with closed cranial windows, we monitored sciatic nerve stimulation (SNS)‐induced PAD in the absence or presence of an A2A blocker (ZM 241385, 10 μM), BKCa blocker (paxilline [PAX], 10 μM), and Kir blocker (BaCl2, 100 μM). Each of these interventions led to a substantial (60–67%) suppression of SNS‐induced PADs, confirming the involvement of A2A receptors and BKCa and Kir 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 BaCl2. On the other hand, the presence of PAX abolished NS1619‐induced PAD, without affecting ADO or KCl‐related PAD. Results suggest that enhancing Kir function via the increased activities of both A2A and BK pathways represents an important mechanism of NVC. We speculate that the Kir‐dependence of the ADO response may involve A2A‐mediated cAMP generation and subsequent phosphorylation‐related potentiation of Kir channel function.