Effects of Dendroaspis natriuretic peptide on delayed rectifier potassium currents and its mechanism

Dendroaspis natriuretic peptide (DNP), a newly-described natriuretic peptide, plays an inhibitory role in smooth muscle motility of the gastrointestinal tract. However, the effect of DNP on delayed rectifier potassium currents IK(V) is still unclear. In this study, we sought to investigate the effect of DNP on IK(V) and its mechanism in gastric antral circular smooth muscle cells using the whole-cell patch-clamp technique. DNP significantly inhibited IK(V) in a concentration-dependent manner. LY83583 (1 µmol/l), a guanylate cyclase inhibitor, significantly impaired DNP-induced inhibition of IK(V). Moreover, DNP-induced inhibition in IK(V) was potentiated by the cyclic guanosine monophosphate (cGMP) sensitive phosphoesterase inhibitor zaparinast (0.1 µmol/l). DNP-induced inhibition of IK(V) was completely blocked by KT5823, an inhibitor of cGMP-dependent protein kinase G(PKG), but not affected by KT-5720, a PKA-specific inhibitor. Taken together, our results suggest that DNP inhibits IK(V) via the cGMP/PKG-dependent signaling axis instead of the cAMP/PKA pathway.