title: Dendroaspis natriuretic peptide regulates the cardiac L-type Ca2+ channel activity by the phosphorylation of α1c proteins.
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 Ca(2+) channels in rabbit ventricular myocytes. DNP inhibited the L-type Ca(2+) current (I(Ca,L)) in a concentration dependent manner with a IC(50) 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 I(Ca,L). The α(1c) subunit of cardiac L-type Ca(2+) 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 Ca(2+) channel activity by phosphorylating the Ca(2+) channel protein via PKG activation.
authors.affiliation: Department of Pharmacology, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Seon-Ah
authors.initials: SA
authors.lastname: Park
authors.forename: Tae-Geun
authors.initials: TG
authors.lastname: Kim
authors.forename: Myung-Kwan
authors.initials: MK
authors.lastname: Han
authors.forename: Ki-Chan
authors.initials: KC
authors.lastname: Ha
authors.forename: Sung-Zoo
authors.initials: SZ
authors.lastname: Kim
authors.forename: Yong-Geun
authors.initials: YG
authors.lastname: Kwak
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004546:Elapid Venoms / Q000378:metabolism* / Q000494:pharmacology; D004789:Enzyme Activation; D006321:Heart; D006352:Heart Ventricles / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins; D032383:Myocytes, Cardiac / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011817:Rabbits
chemical_list: D020746:Calcium Channels, L-Type; D002227:Carbazoles; C075597:Dendroaspis natriuretic peptide; D004546:Elapid Venoms; D036341:Intercellular Signaling Peptides and Proteins; C419385:L-type calcium channel alpha(1C); D010455:Peptides; C073601:KT 5823; D017869:Cyclic GMP-Dependent Protein Kinases; D002118:Calcium