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The cardiac hERG/IKr potassium channel as pharmacological target: structure, function, regulation, and clinical applications.
Investigation of adrenergic mechanisms of hERG channel regulation as well as the development of strategies to enhance hERG currents and to modify intracellular hERG protein processing may provide novel antiarrhythmic options in repolarization disorders.
Deletion of Protein Kinase A Phosphorylation Sites in the HERG Potassium Channel Inhibits Activation Shift by Protein Kinase A*
It is concluded that PKA regulates HerG channel activation, and direct phosphorylation of the HERG channel protein has a functional role that may be important in regulation of cardiac repolarization.
Adrenergic regulation of the rapid component of the cardiac delayed rectifier potassium current, IKr, and the underlying hERG ion channel
Current knowledge on hERG/IKr channel modulation by adrenergic activity is summarized and therapeutic approaches to future effective, more genotype-specific antiarrhythmic therapies are discussed.
Regulation of HERG potassium channel activation by protein kinase C independent of direct phosphorylation of the channel protein.
HERG Potassium Channel Activation Is Shifted by Phorbol Esters via Protein Kinase A-dependent Pathways*
- J. Kiehn, C. Karle, Dierk Thomas, X. Yao, J. Brachmann, W. Kübler
- BiologyThe Journal of Biological Chemistry
- 25 September 1998
The data suggest that mainly PKA is mediating the shift of the HERG activation kinetics, which is known to act by stimulating distinct protein kinase cascades.
Inhibitory effects of the class III antiarrhythmic drug amiodarone on cloned HERG potassium channels
- J. Kiehn, Dierk Thomas, C. Karle, W. Schöls, W. Kübler
- BiologyNaunyn-Schmiedeberg's Archives of Pharmacology
- 5 March 1999
The data suggest that the strong class III antiarrhythmic action of amiodarone is at least partially based upon its acute inhibitory effects on HERG potassium channels, which are one primary target for the pharmacological management of arrhythmias.
Rapid component I(Kr) of the guinea-pig cardiac delayed rectifier K(+) current is inhibited by beta(1)-adrenoreceptor activation, via cAMP/protein kinase A-dependent pathways.
Aquaporin-1 Channel Function Is Positively Regulated by Protein Kinase C*
This is the first study to show that PKC positively regulates both water permeability and ionic conductance of AQP1 channels.
Deficient Zebrafish Ether-à-Go-Go-Related Gene Channel Gating Causes Short-QT Syndrome in Zebrafish Reggae Mutants
With its molecular and pathophysiological concordance to the human arrhythmia syndrome, zebrafish reg represents the first animal model for human short-QT syndrome.