© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Altered phosphorylation and Ca2+-sensitivity of myofilaments in human heart failure
Herzzentrum Göttingen, Kardiologie und Pneumologie, Georg-August Universität Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany
* Corresponding author. Tel.: +49-551-396-351; fax: +49-551-399-804. schiwolf@med.uni-goettingen.de
Received 21 October 2002; accepted 21 October 2002
| The first 150 words of the full text of this article appear below. |
See article by Van der Velden et al. [18] (pages 37–47) in this issue.
β-Adrenergic receptor stimulation in the heart induces a plethora of physiological and biochemical reactions that serve to elevate cardiac output in situations of increased energy demand such as strong muscular exercise, hypoxia, pain, severe emotional stress, or hypoglycemia. The signal transduction cascade after binding of the ligand to the β1-adrenergic receptor involves activation of the stimulatory G-protein (Gs) and of membrane-bound adenylyl cyclase, followed by formation of the second messenger cyclic 3',5'-adenosine monophosphate (cAMP). Phosphorylation of several intracellular target proteins by cAMP-dependent protein kinase (PKA) finally mediates the various consequences of β-adrenergic receptor stimulation on the heart.
In order to elevate cardiac output, myocyte contractility must be enhanced, which can be accomplished by two principal mechanisms: Either by increasing the availability of [Ca2+]i to activate the myofilaments during systole or by increasing the