Signaling model of PKA's involvement in impaired glycogen metabolism during ischemic stroke.

<p>Within astrocytes under physiological conditions, the binding of an agonist to its receptor leads to the activation of G-proteins (α, β and γ subunits), which in turn activate adenylyl cyclase (AC). Active AC then converts ATP to cAMP that binds to the regulatory subunits of tetrameric PKA. This releases free catalytic subunits that phosphorylate phosphorylase kinase b to convert it to active phosphorylase kinase a. Active phosphorylase kinase then phosphorylates GP<i>b</i> to GP<i>a</i> initiating glycogen breakdown to provide energy for associating neurons <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097570#pone.0097570-Rossi1" target="_blank">[4]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097570#pone.0097570-Brown2" target="_blank">[59]</a>. Inhibition of PKA activity during ischemic conditions, however suppresses this downstream signaling cascade that is essential for glycogen metabolism leading to the accumulation of glycogen in astrocytes in the stroke-affected brain.