The Modulation Effects of Calmodulin on Voltage-gated sodium channels
碩士 === 國立臺灣大學 === 動物學研究所 === 100 === Voltage-gated sodium channels (VGSCs) are essential for the initiation and propagation of action potentials in excitable cells. Calmodulin (CaM), a calcium sensor protein, regulates many types of ionic channels by binding to the highly conserved IQ motif at the i...
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ndltd-TW-100NTU053120112015-10-13T21:45:44Z http://ndltd.ncl.edu.tw/handle/13708776272562345638 The Modulation Effects of Calmodulin on Voltage-gated sodium channels 鈣調素對電壓依賴型鈉離子通道的調控之研究 Shao-Han Chang 張邵涵 碩士 國立臺灣大學 動物學研究所 100 Voltage-gated sodium channels (VGSCs) are essential for the initiation and propagation of action potentials in excitable cells. Calmodulin (CaM), a calcium sensor protein, regulates many types of ionic channels by binding to the highly conserved IQ motif at the intracellular C-terminal. Several reports have suggested that CaM has differential binding affinities with peptides containing the IQ motifs of various Na+ channels. However, it is not clear how CaM modulate the Na+ channel activities. In this report, we co-expressed CaM and Nav1.4 in 293T cells and measured the Na+ currents by patch-clamp technique in whole-cell mode. Both CaM and the Ca2+-binding deficient mutant, CaM1234, enhanced the current amplitude without changing the activation and inactivation properties. Elevating the Ca2+ concentration in the pipette solution to 10 μM, CaM and CaM1234 further increased the Na+ current; however, only CaM shortened the recovery time. While with 0.2 μM Ca2+ in the pipette solution, both CaM and CaM1234 enhanced the Na+ currents but had no effect on recovery time. Staining the expression level of Nav1.4 with a specific antibody, the amount of Nav1.4 at the plasma membrane was increaseed by CaM and CaM1234. Mutation in the IQ motif increased the Na+ current and recovery rates. CaM had a similar effect in enhancing the Nav1.1 currents. These findings suggest that CaM modulates VGSCs via the IQ motif in response to intracellular calcium concentration changes. Chien-Yuan Pan 潘建源 2012 學位論文 ; thesis 80 en_US |
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碩士 === 國立臺灣大學 === 動物學研究所 === 100 === Voltage-gated sodium channels (VGSCs) are essential for the initiation and propagation of action potentials in excitable cells. Calmodulin (CaM), a calcium sensor protein, regulates many types of ionic channels by binding to the highly conserved IQ motif at the intracellular C-terminal. Several reports have suggested that CaM has differential binding affinities with peptides containing the IQ motifs of various Na+ channels. However, it is not clear how CaM modulate the Na+ channel activities. In this report, we co-expressed CaM and Nav1.4 in 293T cells and measured the Na+ currents by patch-clamp technique in whole-cell mode. Both CaM and the Ca2+-binding deficient mutant, CaM1234, enhanced the current amplitude without changing the activation and inactivation properties. Elevating the Ca2+ concentration in the pipette solution to 10 μM, CaM and CaM1234 further increased the Na+ current; however, only CaM shortened the recovery time. While with 0.2 μM Ca2+ in the pipette solution, both CaM and CaM1234 enhanced the Na+ currents but had no effect on recovery time. Staining the expression level of Nav1.4 with a specific antibody, the amount of Nav1.4 at the plasma membrane was increaseed by CaM and CaM1234. Mutation in the IQ motif increased the Na+ current and recovery rates. CaM had a similar effect in enhancing the Nav1.1 currents. These findings suggest that CaM modulates VGSCs via the IQ motif in response to intracellular calcium concentration changes.
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author2 |
Chien-Yuan Pan |
author_facet |
Chien-Yuan Pan Shao-Han Chang 張邵涵 |
author |
Shao-Han Chang 張邵涵 |
spellingShingle |
Shao-Han Chang 張邵涵 The Modulation Effects of Calmodulin on Voltage-gated sodium channels |
author_sort |
Shao-Han Chang |
title |
The Modulation Effects of Calmodulin on Voltage-gated sodium channels |
title_short |
The Modulation Effects of Calmodulin on Voltage-gated sodium channels |
title_full |
The Modulation Effects of Calmodulin on Voltage-gated sodium channels |
title_fullStr |
The Modulation Effects of Calmodulin on Voltage-gated sodium channels |
title_full_unstemmed |
The Modulation Effects of Calmodulin on Voltage-gated sodium channels |
title_sort |
modulation effects of calmodulin on voltage-gated sodium channels |
publishDate |
2012 |
url |
http://ndltd.ncl.edu.tw/handle/13708776272562345638 |
work_keys_str_mv |
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