KMID : 0620920120440060363
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Experimental & Molecular Medicine 2012 Volume.44 No. 6 p.363 ~ p.368
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Dendroaspis natriuretic peptide regulates the cardiac L-type Ca2+ channel activity by the phosphorylation of ¥á1c proteins
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Park Seon-Ah
Kim Tae-Geun Han Myung-Kwan Ha Ki-Chan Kim Sung-Zoo Kwak Yong-Geun
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Abstract
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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 ¥ìM). DNP did not affect the voltage dependence of activation and inactivation of ICa,L. The ¥á1c subunit of cardiac L-type Ca2+ channel proteins was phosphorylated by the treatment of DNP (1 ¥ìM), which was completely blocked by KT5823 (1 ¥ìM). Finally, DNP also caused the shortening of action potential duration in rabbit ventricular tissue by 22.3 ¡¾ 4.2% of the control (n = 6), which was completely blocked by KT5823 (1 ¥ìM). These results clearly indicate that DNP inhibits the L-type Ca2+ channel activity by phosphorylating the Ca2+ channel protein via PKG activation.
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KEYWORD
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calcium channels, L-type, cyclic GMP-dependent protein kinases, dendroaspis natriuretic peptide, myocytes, cardiac, rabbits
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