Dendroaspis natriuretic peptide regulates the cardiac L-type Ca2+channel activity by the phosphorylation of α1cproteins

Abstract

Dendroaspis natriuretic peptide (DNP), a new member of the natriuretic peptide family, is structurally similar to atrial, brain, and C-type natriuretic peptides. However, the effects of DNP on the cardiac function are poorly defined. In the present study, we examined the effect of DNP on the cardiac L-type Ca2+ channels in rabbit ventricular myocytes. DNP inhibited the L-type Ca2+ current (ICa,L) in a concentration dependent manner with a IC50 of 25.5 nM, which was blocked by an inhibitor of protein kinase G (PKG), KT5823 (1 µM). DNP did not affect the voltage dependence of activation and inactivation of ICa,L. The α1c subunit of cardiac L-type Ca2+ channel proteins was phosphorylated by the treatment of DNP (1 µM), which was completely blocked by KT5823 (1 µM). Finally, DNP also caused the shortening of action potential duration in rabbit ventricular tissue by 22.3 ± 4.2% of the control (n = 6), which was completely blocked by KT5823 (1 µM). These results clearly indicate that DNP inhibits the L-type Ca2+ channel activity by phosphorylating the Ca2+ channel protein via PKG activation.