Adrenergic regulation of the rapid component of the cardiac delayed rectifier potassium current, I(Kr), and the underlying hERG ion channel.
Ventricular arrhythmias are often precipitated by physical or emotional stress, in particular in patients with ischemic heart disease or hereditary long QT syndrome. Stimulation of the sympathetic nervous system in response to exercise or emotional stress causes activation of cardiac alpha- and beta-adrenoceptors. The rapid component of the delayed rectifier potassium current, I(Kr), and the underlying hERG potassium channel are critical for the regulation of heart rhythm. Recent experimental studies revealed that hERG/I(Kr) currents are modulated by alpha- and beta-adrenergic stimulation, providing a pathophysiological explanation for the increased incidence of arrhythmias during stress. This review summarizes the current knowledge on hERG/I(Kr) channel modulation by adrenergic activity. In addition, therapeutic approaches to future effective, more genotype-specific antiarrhythmic therapies are discussed.
Thomas
Dierk
D
Department of Cardiology, Medical University Hospital Heidelberg, Bergheimer Strasse 58. Dierk_Thomas@med.uni-heidelberg.de
Kiehn
Johann
J
Katus
Hugo A
HA
Karle
Christoph A
CA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D006801:Humans; D008133:Long QT Syndrome / Q000150:complications; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000503:physiopathology
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000889:Anti-Arrhythmia Agents; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta