PMID: 9446694Apr 4, 1998Paper

The inhibitory effect of beta-stimulation on the Na/K pump current in guinea pig ventricular myocytes is mediated by a cAMP-dependent PKA pathway

Pflügers Archiv : European journal of physiology
J GaoG J Baldo

Abstract

The beta-agonist isoproterenol (ISO) reduces the Na/K pump current (Ip) via beta-adrenergic receptors when the intracellular calcium concentration ([Ca2+]i) is below 150 nM [8]. In the present study, the intracellular signaling pathway was investigated with whole-cell patch-clamp of isolated guinea pig ventricular myocytes. The inhibitory effect of ISO could be mimicked by external application of the membrane-permeant cAMP analog chlorophenylthio-cAMP (0.5 mM), the phosphodiesterase inhibitor isobutyl-1-methylxanthine (IBMX, 100 microM), or the adenylyl cyclase activator forskolin (50 microM). Intracellular application of the synthetic peptide inhibitor of protein kinase A (PKA), PKI (5 microM), prevented the effect of ISO. These results suggest that the inhibitory effect of ISO on Ip is mediated via a phosphorylation step induced by a cAMP-dependent PKA pathway. Neither the non-specific protein kinase inhibitor H7 (100 microM) nor the protein phosphatase inhibitor calyculin A (0.5 microM) had any effect on Ip in the absence of ISO. However, H7 could increase Ip and calyculin A could reduce it in the presence of ISO (1 microM and 12 nM respectively). These results indicate that there is a low basal level of phosphorylation whic...Continue Reading

Citations

Sep 8, 2012·Cellular and Molecular Life Sciences : CMLS·W FullerK J Wypijewski
Apr 28, 2004·Cell Calcium·Ursula RavensOttó Hála
Mar 3, 2010·The Journal of Biological Chemistry·Caroline N WhiteHelge H Rasmussen
Nov 30, 2006·Annals of the New York Academy of Sciences·Donald M BersJulie Bossuyt
May 16, 2013·Journal of Molecular and Cellular Cardiology·Davor PavlovicMichael J Shattock
Aug 4, 2007·Progress in Neurobiology·Tamás L Török
Dec 19, 2003·FEMS Microbiology Letters·Yohko Yamada, Masazumi Sameshima
May 28, 2015·Journal of Bacteriology·Zhi-Hui Chen, Pauline Schaap
Jun 8, 2001·News in Physiological Sciences : an International Journal of Physiology Produced Jointly by the International Union of Physiological Sciences and the American Physiological Society·R. T. MathiasY. Wang
Mar 30, 2017·Cellular and Molecular Neurobiology·Megha AmarBirendra Nath Mallick
Oct 3, 2001·Physiological Reviews·H G Glitsch
Aug 28, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Antonella CelliniPetra Eder-Negrin

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