Effects of Dendroaspis Natriuretic Peptide on Calcium-Activated Potassium Current and Its Mechanism

In this study, we sought to investigate the effect of dendroaspis natriuretic peptide (DNP) on calcium-activated potassium current (I K(Ca)) and its mechanism in gastric antral circular smooth muscle cells (SMCs) using the whole-cell patch-clamp technique. DNP concentration-dependently increased macroscopic I K(Ca) and spontaneous transient outward currents (STOCs) in freshly isolated guinea pig gastric antral circular SMCs. The effects of DNP on I K(Ca) and/or STOCs were not blocked by applying calcium-free bath solution or the ryanodine receptor (RyR) antagonist ryanodine (10 microM), but they were inhibited by the inositol triphosphate receptor (IP3R) inhibitor heparin or the guanylate cyclase inhibitor LY83583. Moreover, a DNP-induced increase in STOCs was potentiated by the cyclic guanosine monophosphate (cGMP)-sensitive phosphoesterase inhibitor zaprinast. In conclusion, our results suggest that DNP increases I K(Ca) in gastric antral circular SMCs by increasing cGMP production and activating IP3Rs.