The natriuretic peptides BNP and CNP increase heart rate and electrical conduction by stimulating ionic currents in the sinoatrial node and atrial myocardium following activation of guanylyl cyclase-linked natriuretic peptide receptors

详细信息	查看全文 | 推荐本文 |

• 作者：Jeremy Springer ; John Azer ; Rui Hua ; Courtney Robbins ; Andrew Adamczyk ; Sarah McBoyle ; Mary Beth Bissell ; Robert A. Rose ; ^{robert.rose@dal.ca}
• 关键词：Natriuretic peptides ; Natriuretic peptide receptors ; Electrocardiography ; Sinoatrial node ; Action potential ; Ion channels ; Phosphodiesterase
• 刊名：Journal of Molecular and Cellular Cardiology
• 出版年：2012
• 期刊代码：171_00222828
• 类别：bio
• 出版时间：May, 2012
• 卷：52
• 期：5
• 页码：1122-1134
• 文件大小：1830 K

摘要

Natriuretic peptides (NPs) are best known for their ability to regulate blood vessel tone and kidney function whereas their electrophysiological effects on the heart are less clear. Here, we measured the effects of BNP and CNP on sinoatrial node (SAN) and atrial electrophysiology in isolated hearts as well as isolated SAN and right atrial myocytes from mice. BNP and CNP dose-dependently increased heart rate and conduction through the heart as indicated by reductions in R-R interval, P wave duration and P-R interval on ECGs. In conjunction with these ECG changes BNP and CNP (100 nM) increased spontaneous action potential frequency in isolated SAN myocytes by increasing L-type Ca^2 + current (I_Ca,L) and the hyperpolarization-activated current (I_f). BNP had no effect on right atrial myocyte APs in basal conditions; however, in the presence of isoproterenol (10 nM), BNP increased atrial AP duration and I_Ca,L. Quantitative gene expression and immunocytochemistry data show that all three NP receptors (NPR-A, NPR-B and NPR-C) are expressed in the SAN and atrium. The effects of BNP and CNP on SAN and right atrial myocytes were maintained in mutant mice lacking functional NPR-C receptors and blocked by the NPR-A antagonist A71915 indicating that BNP and CNP function through their guanylyl cyclase-linked receptors. Our data also show that the effects of BNP and CNP are completely absent in the presence of the phosphodiesterase 3 inhibitor milrinone. Based on these data we conclude that NPs can increase heart rate and electrical conduction by activating the guanylyl cyclase-linked NPR-A and NPR-B receptors and inhibiting PDE3 activity.