Inhibition of L-type Ca2+ current by C-type natriuretic peptide in bullfrog atrial myocytes: an NPR-C-mediated effect.
Single atrial myocytes were isolated from the bullfrog heart and studied under current and voltage clamp conditions to determine the electrophysiological effects of the C-type natriuretic peptide (CNP). CNP (10(-8) M) significantly shortened the action potential and reduced its peak amplitude after the application of isoproteronol (10(-7) M). In voltage clamp studies, CNP inhibited isoproteronol-stimulated L-type Ca2+ current (ICa) without any significant effect on the inward rectifier K+ current. The effects of cANF (10(-8) M), a selective agonist of the natriuretic peptide C receptor (NPR-C), were very similar to those of CNP. Moreover, HS-142-1, an antagonist of the guanylyl cyclase-linked NPR-A and NPR-B receptors did not alter the inhibitory effect of CNP on ICa. Inclusion of cAMP in the recording pipette to stimulate ICa at a point downstream from adenylyl cyclase increased ICa, but this effect was not inhibited by cANF. These results provide the first demonstration that CNP can inhibit ICa after binding to NPR-C, and suggest that this inhibition involves a decrease in adenylyl cyclase activity, which leads to reduced intracellular levels of cAMP.
Rose
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RA
Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta, Canada T2N 4N1.
Lomax
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AE
Giles
W R
WR
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006325:Heart Atria / Q000166:cytology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D045283:Natriuretic Agents / Q000494:pharmacology*; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011134:Polysaccharides / Q000494:pharmacology; D011892:Rana catesbeiana; D017461:Receptors, Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000099242:Atrial Natriuretic Factor Receptor B
D020746:Calcium Channels, L-Type; D000242:Cyclic AMP; D006162:Guanylate Cyclase; D045283:Natriuretic Agents; D020098:Natriuretic Peptide, C-Type; D011134:Polysaccharides; D017461:Receptors, Atrial Natriuretic Factor; D000099242:Atrial Natriuretic Factor Receptor B; C072551:HS 142-1; C091715:atrial natriuretic factor receptor A; C073616:atrial natriuretic factor receptor C