Loading...
|
Please use this identifier to cite or link to this item:
http://ntur.lib.ntu.edu.tw/handle/246246/93125
|
| Title: | Characterization of an Lot5-Related Mutation in Kcne1, Y81c: Implications for a Role of Kcne1 Cytoplasmic Domain in I-Ks Channel Function |
| Authors: | 賴凌平
LAI, LING-PING |
| Contributors: | 內科 |
| Keywords: | voltage clamp;mutagenesis;long QT syndrome;slow delayed rectifier K channel |
| Date: | 2006 |
| Issue Date: | 2009-09-29T04:55:20Z |
| Abstract: | BACKGROUND Y81C is a new Long QT-5 (LOT5)-related KCNE1 mutation, which is Located in the post-transmembrane domain( post-TMD) region in close proximity to three other LQT5 mutations (S74L, D76N, and W87R). OBJECTIVE We examine the effects of Y81C on the function and drug sensitivity of the stow delayed rectifier channel (41) formed by KCNE1 with pore-forming KCNQ1 subunits. We also infer a structural basis for the detrimental effects of Y81C on I-Ks function. METHODS Wild-type (WT) and mutant ( harboring Y81C) I-Ks channels are expressed in oocytes or COS-7 cells. Channel function and KCNQ1 protein expression/subcellular distribution are studied by techniques of electrophysiology, biochemistry, and immunocytochemistry. Ab initio structure predictions of KCNE1 cytoplasmic domain are performed by the Robetta server. RESULTS Relative to WT KCNE1, Y81C reduces I-Ks current amplitude and shifts the voltage range of activation to a more positive range. Y81C does not reduce whole-cell KCNQ1 protein Level or interfere with KCNQ1 trafficking to cell surface. Thus, its effects are mediated by altered KCNQ1/KCNE1 interactions in cell surface channels . Importantly, Y81C potentiates the effects of an I-Ks activator. Preserving the aromatic or hydroxyl side chain at position 81 ( Y81F or Y81T) does not prevent the detrimental effects of Y81C. Structure predictions suggest that the post-TMD region of KCNE1 may adopt a helical secondary structure. CONCLUSION We propose that the post-TMD region of KCNE1 interacts with the KCNQ1 channel to modulate I-Ks current amplitude and gating kinetics. Other LQT5 mutations in this region share the Y81C phenotype and probably affect the I, channel function by a similar mechanism. |
| Relation: | HEART RHYTHM v.3 n.9 pp.1031-1040 |
| Appears in Collections: | [醫學系內科] 期刊論文
|
Files in This Item:
There are no files associated with this item.
|
All items in NTUR are protected by copyright, with all rights reserved.
|
