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 |
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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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