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Raf kinase inhibitor protein: lessons of a better way for β‐adrenergic receptor activation in the heart
Author(s) -
Lorenz Kristina,
Rosner Marsha Rich,
Brand Theresa,
Schmitt Joachim P
Publication year - 2017
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp274064
Subject(s) - stimulation , heart failure , myofilament , receptor , myocyte , endogeny , medicine , cardiac function curve , protein kinase a , endocrinology , kinase , cardiology , microbiology and biotechnology , biology
Stimulation of β‐adrenergic receptors (βARs) provides the most efficient physiological mechanism to enhance contraction and relaxation of the heart. Activation of βARs allows rapid enhancement of myocardial function in order to fuel the muscles for running and fighting in a fight‐or‐flight response. Likewise, βARs become activated during cardiovascular disease in an attempt to counteract the restrictions of cardiac output. However, long‐term stimulation of βARs increases the likelihood of cardiac arrhythmias, adverse ventricular remodelling, decline of cardiac performance and premature death, thereby limiting the use of βAR agonists in the treatment of heart failure. Recently the endogenous Raf kinase inhibitor protein (RKIP) was found to activate βAR signalling of the heart without adverse effects. This review will summarize the current knowledge on RKIP‐driven compared to receptor‐mediated signalling in cardiomyocytes. Emphasis is given to the differential effects of RKIP on β 1 ‐ and β 2 ‐ARs and their downstream targets, the regulation of myocyte calcium cycling and myofilament activity.