KCNE1 enhances phosphatidylinositol 4,5-bisphosphate (PIP2) sensitivity of IKs to modulate channel activity
| Autor: | Jianmin Cui, Dick Wu, Michael Guan, Yang Li, Jingyi Shi, Brett Virgin-Downey, Mark A. Zaydman |
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| Rok vydání: | 2011 |
| Předmět: |
Phosphatidylinositol 4
5-Diphosphate Patch-Clamp Techniques Potassium Channels Protein subunit Mutant Molecular Sequence Data Biology Xenopus Proteins medicine.disease_cause chemistry.chemical_compound Xenopus laevis medicine Animals Humans Patch clamp Phosphatidylinositol Amino Acid Sequence Ion channel Ions Mutation Multidisciplinary Sequence Homology Amino Acid Biological Sciences Lipids Potassium channel Protein Structure Tertiary Long QT Syndrome Biochemistry chemistry Phosphatidylinositol 4 5-bisphosphate Potassium Channels Voltage-Gated KCNQ1 Potassium Channel Biophysics lipids (amino acids peptides and proteins) |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 108(22) |
| ISSN: | 1091-6490 |
| Popis: | Phosphatidylinositol 4,5-bisphosphate (PIP 2 ) is necessary for the function of various ion channels. The potassium channel, I Ks , is important for cardiac repolarization and requires PIP 2 to activate. Here we show that the auxiliary subunit of I Ks , KCNE1, increases PIP 2 sensitivity 100-fold over channels formed by the pore-forming KCNQ1 subunits alone, which effectively amplifies current because native PIP 2 levels in the membrane are insufficient to activate all KCNQ1 channels. A juxtamembranous site in the KCNE1 C terminus is a key structural determinant of PIP 2 sensitivity. Long QT syndrome associated mutations of this site lower PIP 2 affinity, resulting in reduced current. Application of exogenous PIP 2 to these mutants restores wild-type channel activity. These results reveal a vital role of PIP 2 for KCNE1 modulation of I Ks channels that may represent a common mechanism of auxiliary subunit modulation of many ion channels. |
| Databáze: | OpenAIRE |
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