The auxiliary subunit KCNE1 regulates KCNQ1 channel response to sustained calcium-dependent PKC activation

Autor: Xiaorong Xu Parks, Coeli M. Lopes, Chen Braun, Haani Qudsi
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Potassium Channels
Physiology
Cell Membranes
030204 cardiovascular system & hematology
Biochemistry
Ion Channels
0302 clinical medicine
Animal Cells
Medicine and Health Sciences
Myocyte
Myocytes
Cardiac
Post-Translational Modification
Phosphorylation
Internalization
Protein Kinase C
media_common
Cardiomyocytes
Multidisciplinary
Chemistry
Physics
Heart
Potassium channel
Stoichiometry
Cell biology
Electrophysiology
Potassium Channels
Voltage-Gated
Physical Sciences
KCNQ1 Potassium Channel
cardiovascular system
Medicine
Cell lines
Female
Cellular Structures and Organelles
Cellular Types
Anatomy
Biological cultures
Research Article
congenital
hereditary
and neonatal diseases and abnormalities
media_common.quotation_subject
Protein subunit
Science
Muscle Tissue
Biophysics
Neurophysiology
Transfection
Sudden death
03 medical and health sciences
Homomeric
Animals
Humans
Molecular Biology Techniques
Molecular Biology
Protein kinase C
Muscle Cells
HEK 293 cells
Biology and Life Sciences
Proteins
Cell Biology
Rats
Research and analysis methods
030104 developmental biology
Biological Tissue
HEK293 Cells
Mutation
Cardiovascular Anatomy
Calcium
Neuroscience
Zdroj: PLoS ONE
PLoS ONE, Vol 15, Iss 8, p e0237591 (2020)
ISSN: 1932-6203
Popis: The slow cardiac delayed rectifier current (IKs) is formed by KCNQ1 and KCNE1 subunits and is one of the major repolarizing currents in the heart. Decrease of IKs currents either due to inherited mutations or pathological remodeling is associated with increased risk for cardiac arrhythmias and sudden death. Ca2+-dependent PKC isoforms (cPKC) are chronically activated in heart disease and diabetes. Recently, we found that sustained stimulation of the calcium-dependent PKCβII isoform leads to decrease in KCNQ1 subunit membrane localization and KCNQ1/KCNE1 channel activity, although the role of KCNE1 in this regulation was not explored. Here, we show that the auxiliary KCNE1 subunit expression is necessary for channel internalization. A mutation in a KCNE1 phosphorylation site (KCNE1(S102A)) abolished channel internalization in both heterologous expression systems and cardiomyocytes. Altogether, our results suggest that KCNE1(S102) phosphorylation by PKCβII leads to KCNQ1/KCNE1 channel internalization in response to sustained PKC stimulus, while leaving KCNQ1 homomeric channels in the membrane. This preferential internalization is expected to have strong impact on cardiac repolarization. Our results suggest that KCNE1(S102) is an important anti-arrhythmic drug target to prevent IKs pathological remodeling leading to cardiac arrhythmias.
Databáze: OpenAIRE
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