Figure 2.

Schematic overview of ion channel modulation by S-nitrosylation and cGMP-dependent mechanisms. Several ion channel families are modulated by redox-sensitive mechanisms including S-nitrosylation. Other channel families are modified by both redox-sensitive and direct cGMP-dependent signaling (in addition to protein kinase G (PKG) activation with subsequent protein phosphorylation). A combination of the above signaling and modulation of different or multiple residues within one channel protein may lead to graded or opposing effects on channel conductances or kinetics with diverse outcomes for neuronal excitabilities. These complex modulatory effects depend on the redox state on the cell, amount of available NO and activities of mechanisms, which reverse the signaling, such as de-/trans-nitrosylation, breakdown of cGMP via phosphodiesterases (PDE), or dephosphorylation by phosphatases