B-type natriuretic peptide (BNP) attenuates the L-type calcium current and regulates ventricular myocyte function

• Published in: Regulatory peptides Vol. 151; no. 1; pp. 95 - 105
• Main Authors: Sodi, R., Dubuis, E., Shenkin, A., Hart, G.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 29.11.2008; Elsevier
• Subjects: Action potential; Animals; B-type natriuretic peptide; Biological and medical sciences; Calcium Channels, L-Type - drug effects; Calcium Channels, L-Type - metabolism; Calcium current; Calcium transients; Electrophysiology; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Male; Models, Cardiovascular; Myocardial Contraction - drug effects; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - physiology; Natriuretic Peptide, Brain - pharmacology; Patch-Clamp Techniques; Rats; Rats, Wistar; Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism; Ventricular myocytes; Vertebrates: endocrinology; Action potential; B-type natriuretic peptide; Calcium transients; Ventricular myocytes; Calcium current; Heart; Calcium; Peptides; Electrophysiology; Ionic current; Inorganic element; Myocyte; Circulatory system
• ISSN: 0167-0115; 1873-1686
• DOI: 10.1016/j.regpep.2008.06.006

A fundamental question in physiology is how hormones regulate the functioning of a cell or organ. It was therefore the aim of this study to investigate the effect(s) of BNP-32 on calcium handling by ventricular myocytes obtained from the rat left ventricle. We specifically tested the hypothesis that BNP-32 decreased the L-type calcium current ( I Ca,L). Perforated patch clamp technique was used to record I Ca,L and action potential (AP) in voltage and current clamp mode, respectively. Myocyte shortening was measured using a photodiode array edge-detection system and intracellular calcium transients were measured by fluorescence photometry. Western blotting was used to determine the relative change in the expression of proteins. At the concentrations tested, BNP-32 significantly decreased cell shortening in a dose-dependent manner; increased the phase II slope of the AP by 53.0%; increased the APD 50 by 16.9%; reduced the I Ca,L amplitude with a 22.9% decrease in the peak amplitude and reduced Ca 2+-dependent inactivation; increased the V 1/2 activation of the L-type calcium channel by 51.1% and decreased V 1/2 inactivation by 31.8%; and, intracellular calcium transient amplitude was significantly decreased by 32.0%, whereas the time to peak amplitude and T 1/2 were both significantly increased by 38.7% and 89.4% respectively. Sarcoplasmic reticulum Ca 2+-ATPase (SERCA2a) protein expression was reduced by BNP-32. These data suggest that BNP-32 regulates ventricular myocyte function by attenuating I Ca,L, altering the AP and reducing SERCA2a activity and/or expression. This study suggests a novel constitutive mechanism for the autocrine action of BNP on the L-type calcium channel in ventricular myocytes.