Interactions between adenosine and K+channel-related pathways in the coupling of somatosensory activation and pial arteriolar dilation

Abstract

Multiple, perhaps interactive, mechanisms participate in the linkage between increased neural activity and cerebral vasodilation. In the present study, we assessed whether neural activation-related pial arteriolar dilation (PAD) involved interactions among adenosine (Ado) A2receptors (A2Rs), large-conductance Ca2+-operated K+(BKCa) channels, and inward rectifier K+(Kir) channels. In rats with closed cranial windows, we monitored sciatic nerve stimulation (SNS)-induced PAD in the absence or presence of pharmacological blockade of A2Rs (ZM-241385), ecto-5′-nucleotidase (α,β-methylene-adenosine diphosphate), BKCachannels (paxilline), and Kirchannels (BaCl2). Individually, these interventions led to 53–66% reductions in SNS-induced PADs. Combined applications of these blockers led to little or no further repression of SNS-induced PADs, suggesting interactions among A2Rs and K+channels. In the absence of SNS, BaCl2blockade of Kirchannels produced 52–80% reductions in Ado and NS-1619 (BKCachannel activator)-induced PADs. In contrast, paxilline blockade of BKCachannels was without effect on dilations elicited by KCl (Kirchannel activator) and Ado suffusions, indicating that Ado- and NS-1619-associated PADs involved Kirchannels. In addition, targeted ablation of the superficial glia limitans was associated with a selective 60–80% loss of NS-1619 responses, suggesting that the BKCachannel participation (and paxilline sensitivity) derived largely from channels within the glia limitans. Additionally, blockade of either PKA or adenylyl cyclase caused markedly attenuated pial arteriolar responses to SNS and, in the absence of SNS, responses to Ado, KCl, and NS-1619. These findings suggested a key, possibly permissive, role for A2R-linked cAMP generation and PKA-induced K+channel phosphorylation in somatosensory activation-evoked PAD.