PKC modulation of neurovascular coupling

Abstract

Protein kinase C (PKC) has been shown to phosphorylate several ion channels involved in neurovascular coupling. Therefore, we sought to assess whether PKC is involved in the regulation of neurally‐evoked pial arteriolar dilation. Using a closed cranial window technique for vessel diameter monitoring, we studied pial arteriolar dilations during sciatic nerve stimulation (SNS) in rats. Topical application of the PKC non‐isoform specific agonist phorbol 12,13‐dibutyrate (PdBu), was able to significantly reduce the dilatory response to SNS. We previously found that a substantial portion of SNS‐induced arteriolar dilation is mediated by the release of K+ from glia limitans large‐conductance Ca2+‐operated K+ (BKCa) channels, which, in turn, activate pial arteriolar smooth muscle inward rectifier K+ (Kir) channels. Both, BKCa and Kir channels can be phosphorylated by PKC. Thus, we compared BKCa and Kir ‐induced vasodilating function in the presence and absence of PdBu. The reactivity to topical applications of the BKCa channel opener, NS1619, and the Kir agonist, KCl, was found to be significantly decreased when the drugs were co‐applied with PdBu. However, responses to adenosine, SNAP, and hypercapnia were not affected by PdBu suffusion, ruling out the possibility of non‐specific effects. These results point to a significant involvement of PKC in regulating the gliovascular mechanisms underlying neurovascular couplingThis work was supported by grant 3‐2008‐462 from Juvenile Diabetes Research Foundation (JDRF) to F.V., NIH grant HL088259 to D.A.P. and American Heart Association grant 0635337N to H.L. Xu