Action mechanisms of protein kinases and KMUP-1 on store-operated channels in pulmonary artery smooth muscle cells
碩士 === 高雄醫學大學 === 藥理學研究所 === 97 === Store-operated channels (SOCs) are Ca2+-permeable cation channels located in the plasma membrane which are activated by agents that deplete intracellular Ca2+ stores, such as the sarcoplasmic reticulum (SR) or endoplasmic reticulum (ER). Capacitative calcium entry...
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ndltd-TW-097KMC055500042015-11-13T04:09:13Z http://ndltd.ncl.edu.tw/handle/35187268889337674873 Action mechanisms of protein kinases and KMUP-1 on store-operated channels in pulmonary artery smooth muscle cells 蛋白激酶和KMUP-1對肺動脈平滑肌細胞之鈣池調控鈣離子通道的作用機轉 I-Shan Chen 陳以珊 碩士 高雄醫學大學 藥理學研究所 97 Store-operated channels (SOCs) are Ca2+-permeable cation channels located in the plasma membrane which are activated by agents that deplete intracellular Ca2+ stores, such as the sarcoplasmic reticulum (SR) or endoplasmic reticulum (ER). Capacitative calcium entry (CCE) via the SOC is an important mechanism for regulating intracellular Ca2+ concentration. In vascular smooth muscles, SOCs contribute to vasoconstriction, cell growth and proliferation. Our previous studies demonstrated that KMUP-1 possesses a cGMP-dependent relaxation in pulmonary artery smooth muscle cells (PASMCs). In this study, we first investigated the action mechanisms of protein kinase and KMUP-1 on SOCs in freshly dispersed PAMSCs with patch-clamp techniques. In whole-cell recording, selective SOC blocker SKF-96365 (50 μM) reduced SOC current evoked by the Ca2+-ATPase inhibitor cyclopiazonic acid (CPA, 10 μM). In inside-out configuration, the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA, 10 μM) stimulated SOC activity. Bath application of 10 μM inositol 1,4,5- triphosphate (Ins(1,4,5)P3) enhanced channel activity induced by 10 μM PMA. In cell-attached configuration, the protein kinase G (PKG) inhibitor KT5823 (3 μM) and the protein kinase A (PKA) inhibitor H-89 (10 μM) also stimulated SOC activity. With whole-cell recording, KMUP-1 (10 μM) reduced SOC current evoked by CPA (10 μM) and KT5823 (3 μM). In light of these results suggested that SOCs in PASMCs are activated by stimulation of PKC and inhibition of PKG and PKA. KMUP-1 inhibits SOC activity that could be involved in modulation of PKG in PASMCs. Bin-Nan Wu 吳炳男 2009 學位論文 ; thesis 58 zh-TW |
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碩士 === 高雄醫學大學 === 藥理學研究所 === 97 === Store-operated channels (SOCs) are Ca2+-permeable cation channels located in the plasma membrane which are activated by agents that deplete intracellular Ca2+ stores, such as the sarcoplasmic reticulum (SR) or endoplasmic reticulum (ER). Capacitative calcium entry (CCE) via the SOC is an important mechanism for regulating intracellular Ca2+ concentration. In vascular smooth muscles, SOCs contribute to vasoconstriction, cell growth and proliferation.
Our previous studies demonstrated that KMUP-1 possesses a cGMP-dependent relaxation in pulmonary artery smooth muscle cells (PASMCs). In this study, we first investigated the action mechanisms of protein kinase and KMUP-1 on SOCs in freshly dispersed PAMSCs with patch-clamp techniques.
In whole-cell recording, selective SOC blocker SKF-96365 (50 μM) reduced SOC current evoked by the Ca2+-ATPase inhibitor cyclopiazonic acid (CPA, 10 μM). In inside-out configuration, the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA, 10 μM) stimulated SOC activity. Bath application of 10 μM inositol 1,4,5- triphosphate (Ins(1,4,5)P3) enhanced channel activity induced by 10 μM PMA. In cell-attached configuration, the protein kinase G (PKG) inhibitor KT5823 (3 μM) and the protein kinase A (PKA) inhibitor H-89 (10 μM) also stimulated SOC activity. With whole-cell recording, KMUP-1 (10 μM) reduced SOC current evoked by CPA (10 μM) and KT5823 (3 μM).
In light of these results suggested that SOCs in PASMCs are activated by stimulation of PKC and inhibition of PKG and PKA. KMUP-1 inhibits SOC activity that could be involved in modulation of PKG in PASMCs.
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author2 |
Bin-Nan Wu |
author_facet |
Bin-Nan Wu I-Shan Chen 陳以珊 |
author |
I-Shan Chen 陳以珊 |
spellingShingle |
I-Shan Chen 陳以珊 Action mechanisms of protein kinases and KMUP-1 on store-operated channels in pulmonary artery smooth muscle cells |
author_sort |
I-Shan Chen |
title |
Action mechanisms of protein kinases and KMUP-1 on store-operated channels in pulmonary artery smooth muscle cells |
title_short |
Action mechanisms of protein kinases and KMUP-1 on store-operated channels in pulmonary artery smooth muscle cells |
title_full |
Action mechanisms of protein kinases and KMUP-1 on store-operated channels in pulmonary artery smooth muscle cells |
title_fullStr |
Action mechanisms of protein kinases and KMUP-1 on store-operated channels in pulmonary artery smooth muscle cells |
title_full_unstemmed |
Action mechanisms of protein kinases and KMUP-1 on store-operated channels in pulmonary artery smooth muscle cells |
title_sort |
action mechanisms of protein kinases and kmup-1 on store-operated channels in pulmonary artery smooth muscle cells |
publishDate |
2009 |
url |
http://ndltd.ncl.edu.tw/handle/35187268889337674873 |
work_keys_str_mv |
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