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

抄録

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 μM), 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.