Figure 10.
Possible pathways involved in KATP channel activation by NO and sites of action of modulators. SNAP exogenously releases NO that might have activated sGC by diffusion into the cytosol. sGC in other tissues generates endogenous cGMP, which may further activate PKG in order to produce downstream effects on the channel. However, the results of this study imply that sGC is not active in DRG neurons. Dashed arrows indicate also that the indirect NO/sGC/cGMP/PKG pathway is not active in DRG neurons, because ODQ, a specific sGC inhibitor, and KT 5823, a specific PKG inhibitor, fail to block it (red arrows). In contrast, exogenous membrane permeable 8-Br-cGMP (blue arrow) activates KATP channels via PKG. Solid arrow indicates that NO most likely activates KATP channels via S-nitrosylation on the NBD1 within the SUR1 subunit. This direct pathway is prevented by thiol-alkylating, or reversed or thiol-reducing agents (NEM or DTT, respectively; red arrow).