Figure 5.
Regulation by ATP of the mode-1 LV exocytotic pathway in beta cells. (A) Semilogarithmic plots of amperometric latency histograms. Data are from cells perfused with 3 mM ATP[γS] (open circles), 3 mM ATP (open triangles), 0 mM ATP (open squares), or AMP-PNP (closed diamonds), as well as from those pretreated with Rp-cAMP before perfusion with 3 mM ATP (closed squares). Blue and dashed lines indicate the mode-1 and mode-2 components, respectively. (B) The mode-1 LVs, which constitute 90% of fusion-ready LVs in resting beta cells, require cAMP-dependent phosphorylation in addition to Ca2+ for the final triggering of exocytosis. Both adenylate cyclase and PKA confer ATP dependence on mode-1 exocytosis and act as the final ATP sensor. This model predicts that the ATP sensitivity of exocytosis can be modulated by the activities of various components of the cAMP signaling cascade (blue), including G proteins (Gs or Gi) and G protein coupled receptors (Rs or Ri).