Inhibition of L-type Ca current by C-type natriuretic peptide in bullfrog atrial myocytes: an NPR-C-mediated effect

Rose, R. A., A. E. Lomax, and W. R. Giles. Inhibition of L-type Ca2 current by C-type natriuretic peptide in bullfrog atrial myocytes: an NPR-C-mediated effect. Am J Physiol Heart Circ Physiol 285: H2454–H2462, 2003. First published July 24, 2003; 10.1152/ajpheart.00388.2003.—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.