Exp Mol Med.  2012 Jun;44(6):363-368.

Dendroaspis natriuretic peptide regulates the cardiac L-type Ca2+ channel activity by the phosphorylation of alpha1c proteins

• Park SA
• Kim TG
• Han MK
• Ha KC
• Kim SZ
• Kwak YG

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 microM). DNP did not affect the voltage dependence of activation and inactivation of ICa,L. The alpha1c subunit of cardiac L-type Ca2+ channel proteins was phosphorylated by the treatment of DNP (1 microM), which was completely blocked by KT5823 (1 microM). 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 microM). These results clearly indicate that DNP inhibits the L-type Ca2+ channel activity by phosphorylating the Ca2+ channel protein via PKG activation.

Keyword

calcium channels, L-type; cyclic GMP-dependent protein kinases; dendroaspis natriuretic peptide; myocytes, cardiac; rabbits

MeSH Terms

Action Potentials/drug effects
Animals
Biological Transport/drug effects
Calcium/metabolism
Calcium Channels, L-Type/*metabolism
Carbazoles/pharmacology
Cells, Cultured
Cyclic GMP-Dependent Protein Kinases/antagonists & inhibitors
Elapid Venoms/*metabolism/pharmacology
Enzyme Activation
Heart
Heart Ventricles/drug effects
Myocytes, Cardiac/drug effects
Patch-Clamp Techniques
Peptides/*metabolism/pharmacology
Phosphorylation/drug effects
Rabbits