Cyclic GMP‐mediated inhibition of L‐type Ca2+ channel activity by human natriuretic peptide in rabbit heart cells

• Published in: British journal of pharmacology 1995-03, Vol.114 (5), p.1076-1082
• Main Authors: Tohse, Noritsugu, Nakaya, Haruaki, Kanno, Youji Takeda & Morio
• Format: Article
• Language: English
• Subjects: 1-Methyl-3-isobutylxanthine - pharmacology; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology; 8-Bromo Cyclic Adenosine Monophosphate - pharmacology; Animals; Atrial Natriuretic Factor - pharmacology; Atrial natriuretic peptide; Biological and medical sciences; Calcium Channel Blockers - pharmacology; Calcium Channels - metabolism; cardiomyocyte; cyclic GMP; Cyclic GMP - physiology; Fundamental and applied biological sciences. Psychology; Heart; Heart - drug effects; Heart Ventricles - cytology; Heart Ventricles - drug effects; Heart Ventricles - metabolism; Humans; L‐type Ca2+ channel; Myocardium - cytology; Myocardium - metabolism; patch clamp; Patch-Clamp Techniques; Rabbits; Vertebrates: cardiovascular system
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1995.tb13316.x

1 Effects of atrial natriuretic peptide (ANP) on the L‐type Ca2+ channels were examined in rabbit isolated ventricular cells by use of whole‐cell and cell‐attached configurations of the patch clamp methods. ANP produced a concentration‐dependent decrease (10–100 nm) in amplitude of a basal Ca2+ channel current. 2 The inactive ANP (methionine‐oxidized ANP, 30 nm) failed to decrease the current. 3 8‐Bromo‐cyclic GMP (300 μm), a potent activator of cyclic GMP‐dependent protein kinase (PKG), produced the same effects on the basal Ca2+ channel current as those produced by ANP. The cyclic GMP‐induced inhibition of the Ca2+ channel current was still evoked in the presence of 1‐isobutyl‐3‐methyl‐xanthine, an inhibitor of phosphodiesterase. ANP failed to produce inhibition of the Ca2+ channel current in the presence of 8‐bromo‐cyclic GMP. 4 In the single channel recording, ANP and 8‐bromo‐cyclic GMP also inhibited the activities of the L‐type Ca2+ channels. Both agents decreased the open probability (NP0) without affecting the unit amplitude. 5 The present results suggest that ANP inhibits the cardiac L‐type Ca2+ channel activity through the intracellular production of cyclic GMP and then activation of PKG.