cGMP-stimulated cyclic nucleotide phosphodiesterase regulates the basal calcium current in human atrial myocytes

The Journal of Clinical Investigation
M Rivet-BastideRodolphe Fischmeister

Abstract

EHNA (Erythro-9-[2-hydroxy-3-nonyl]adenine) is a wellknown inhibitor of adenosine deaminase. Recently, EHNA was shown to block the activity of purified soluble cGMPstimulated phosphodiesterase (PDE2) from frog, human, and porcine heart with an apparent Ki value of approximately 1 microM and with negligible effects on Ca2+/calmodulin PDE (PDE1), cGMP-inhibited PDE (PDE3), and low Km cAMP-specific PDE (PDE4) (Méry, P.F., C. Pavoine, F. Pecker, and R. Fischmeister. 1995. Mol. Pharmacol. 48:121-130; Podzuweit, T., P. Nennstiel, and A. Muller. 1995. Cell. Signalling. 7:733- 738). To investigate the role of PDE2 in the regulation of cardiac L-type Ca2+ current (ICa), we have examined the effect of EHNA on ICa in freshly isolated human atrial myocytes. Extracellular application of 0.1-10 microM EHNA induced an increase in the amplitude of basal ICa ( approximately 80% at 1 microM) without modification of the current-voltage or inactivation curves. The maximal stimulatory effect of EHNA on ICa was comparable in amplitude with the maximal effect of isoprenaline (1 microM), and the two effects were not additive. The effect of EHNA was not a result of adenosine deaminase inhibition, since 2'-deoxycoformycin (1-30 microM), another adenosin...Continue Reading

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Citations

Jul 16, 2010·Journal of Cardiovascular Translational Research·Clint L Miller, Chen Yan
Jun 2, 2005·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·Rodolphe FischmeisterGrégoire Vandecasteele
Mar 1, 2006·Progress in Biophysics and Molecular Biology·Fabien BretteLaurent Sallé
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Jun 2, 2012·Journal of Cardiovascular Pharmacology·Emine Demirel-YilmazMehmet Kursat Derici
Aug 18, 2009·The Journal of Pharmacology and Experimental Therapeutics·Anbrin MasoodJames M O'Donnell
May 3, 2006·Circulation·Liliana R V CastroRodolphe Fischmeister
Aug 16, 2008·The Journal of Clinical Investigation·V Arvydas SkeberdisRodolphe Fischmeister
Jul 2, 2003·Bioscience, Biotechnology, and Biochemistry·Noriyuki YanakaKenji Omori
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Sep 12, 2009·Journal of Molecular and Cellular Cardiology·Stéphane N HatemElise Balse
Dec 18, 2015·The Journal of Physiological Sciences : JPS·Rimantas TreinysVytenis Arvydas Skeberdis
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