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Rapid component I(Kr) of cardiac delayed rectifier potassium currents in guinea-pig is inhibited by alpha(1)-adrenoreceptor activation via protein kinase A and protein kinase C-dependent pathways
- Source :
- European journal of pharmacology. 608(1-3)
- Publication Year :
- 2008
-
Abstract
- Ventricular tachyarrhythmias are often precipitated by physical or emotional stress, indicating a link between increased adrenergic stimulation and cardiac ion channel activity. Human ether-a-go-go related gene (hERG) potassium channels conduct the rapid component of delayed rectifier potassium current, I(kr), a crucial component for action potential repolarization. To evaluate the correlation between increased alpha(1)-adrenergic activity and the rapid component of cardiac I(kr), whole-cell patch-clamp recording was performed in isolated guinea-pig ventricular myocytes. Stimulation of alpha(1)-adrenoceptors using phenylephrine (0.1 nM-100 microM) reduced I(kr) current in a dose-dependent manner at 37 degrees C. Phenylephrine (0.1 microM) reduced I(kr) current to 66.83+/-3.16%. Chelerythrine (1 microM), a specific inhibitor of protein kinase C (PKC) completely inhibited the changes in I(kr) trigged by 0.1 microM phenylephrine. KT5720 (2.5 microM), a specific inhibitor of protein kinase A (PKA) partially inhibited the current decrease induced by 0.1 microM phenylephrine. Both chelerythrine and KT5720 drastically reduced the phenylephrine-induced effects, indicating possible involvement of PKC and PKA in the alpha(1)-adrenergic inhibition of I(kr). Our data suggest a link between I(kr) and the alpha(1)-adrenoceptor, involving activation of PKC and PKA in arrhythmogenesis.
- Subjects :
- medicine.medical_specialty
Patch-Clamp Techniques
Heart Ventricles
hERG
Guinea Pigs
Carbazoles
Stimulation
Pharmacology
chemistry.chemical_compound
Phenylephrine
Internal medicine
Receptors, Adrenergic, alpha-1
medicine
Animals
Myocytes, Cardiac
Pyrroles
Enzyme Inhibitors
Potassium Channels, Inwardly Rectifying
Protein kinase A
Protein kinase C
Protein Kinase C
Benzophenanthridines
biology
Dose-Response Relationship, Drug
KT5720
Cyclic AMP-Dependent Protein Kinases
Potassium channel
Electrophysiology
Kinetics
Endocrinology
Chelerythrine
chemistry
biology.protein
Potassium
medicine.drug
Subjects
Details
- ISSN :
- 18790712
- Volume :
- 608
- Issue :
- 1-3
- Database :
- OpenAIRE
- Journal :
- European journal of pharmacology
- Accession number :
- edsair.doi.dedup.....1520695f6ef1ea5c37b04dbdf5073b30