Figure 3.

Signal transduction that epithelium sodium channels involved in. Osteoblast exposure to fluid shear stress leads to influx of sodium. Transmembrane potential is decreased leading to stimulation of voltage-sensitive calcium channel accompanying with calcium influx. An initiation of nitride oxide synthesis may require calcium activation of nitride oxide synthases. For one thing, nitride oxide activates soluble guanylate cyclase and the resulting cyclic guanosine monophosphate activates cyclic guanosine monophosphate-dependent protein kinase II, which phosphorylates substrates leading to activation of the MEK/Erk pathway.[77,78] Extracellular nitride oxide from endothelium e.g., may also stimulate MEK/Erk pathway. For another, activated cyclic guanosine monophosphate-dependent protein kinase II may also enhance expression of epithelium sodium channels. PGE2 derived from cyclooxygenase-2 forms a regulation loop with bone morphogenetic protein/Smad family.