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

Paisansathan C, Xu H, Vetri F, Hernandez M, Pelligrino DA. Interactions between adenosine and K+ channel-related pathways in the coupling of somatosensory activation and pial arteriolar dilation. Am J Physiol Heart Circ Physiol 299: H2009-H2017, 2010. First published October 1, 2010; doi: 10.1152/ajpheart.00702.2010.-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) A(2) receptors (A(2)Rs), large-conductance Ca2+-operated K+ (BKCa) channels, and inward rectifier K+ (K-ir) channels. In rats with closed cranial windows, we monitored sciatic nerve stimulation (SNS)-induced PAD in the absence or presence of pharmacological blockade of A(2)Rs (ZM-241385), ecto-5'-nucleotidase (alpha, beta-methylene-adenosine diphosphate), BKCa channels (paxilline), and K-ir channels (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 A(2)Rs and K+ channels. In the absence of SNS, BaCl2 blockade of K-ir channels produced 52-80% reductions in Ado and NS-1619 (BKCa channel activator)-induced PADs. In contrast, paxilline blockade of BKCa channels was without effect on dilations elicited by KCl (K-ir channel activator) and Ado suffusions, indicating that Ado-and NS-1619-associated PADs involved K-ir channels. In addition, targeted ablation of the superficial glia limitans was associated with a selective 60-80% loss of NS-1619 responses, suggesting that the BKCa channel 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 A(2)R-linked cAMP generation and PKA-induced K+ channel phosphorylation in somatosensory activation-evoked PAD.