Ca^<2+> Entry Channels in Rat Thoracic Aortic Smooth Muscle Cells Activated by Endothelin-1
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概要
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The contraction of the rat aorta induced by endothelin-1 (ET-1) requires entry of extracellur Ca2+, but involvement of voltage-operated Ca2+ channel is minor. Using whole-cell recordings of patch-clamp and monitoring of the intracellular free Ca2+ concentration ([Ca2+]i), we characterized Ca2+ entry channels in A7r5 cells activated by ET-1. ET-1 activates three types of voltage-independent Ca2+ entry channels: two types of Ca2+-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and a store-operated Ca2+ channel (SOCC). Furthermore, it was found that these channels can be pharmacologically discriminated using Ca2+ channel blockers such as SK&F 96365 and LOE 908. NSCC-1 is resistant to SK&F 96365, but sensitive to LOE 908, whereas NSCC-2 is sensitive to both SK&F 96365 and LOE 908. SOCC is sensitive to SK&F 96365, but resistant to LOE 908. Using these channel blockers, we analyzed Ca2+ entry channels involved in the ET-1-induced contractions of rat thoracic aorta and increases in [Ca2+]i of single smooth muscle cells. The responses to lower concentrations of ET-1 (≤0.1 nM) were abolished by either SK&F 96365 or LOE 908 alone. In contrast, the responses to higher concentrations of ET-1 (≥1 nM) were suppressed by SK&F 96365 or LOE 908 to about 10% and 35% of controls, respectively, and abolished by combined treatment with SK&F 96365 and LOE 980. These results show that the responses of rat aorta to lower concentrations of ET-1 involve only one Ca2+ channel that is sensitive to SK&F 96365 and LOE 908 (NSCC-2), whereas those to higher concentrations of ET-1 involve NSCC-1, NSCC-2 and SOCC, contributing 10%, 55% and 35%, respectively, to total Ca2+ entry.
- 社団法人 日本薬理学会の論文
- 1999-08-01
著者
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三輪 聡一
北海道大学 大学院医学研究科 細胞薬理学分野
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Okamoto Yasuo
Department Of Biochemistry Kagawa University Faculty Of Medicine
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Miwa Soichi
Department Of Cellular Pharmacology Hokkaido University Graduate School Of Medicine
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Masaki Tomoh
National Cardiovascular Center Research Institute
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Okamoto Yasuo
Departments Of Pharmacology Kyoto University Faculty Of Medicine
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IWAMURO Yasushi
Department of Neurosurgery,Kokura Memorial Hospital,Kitakyushu,Fukuoka
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Iwamuro Yasushi
Department Of Neurosurgery Fukui Red Cross Hospital
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Iwamuro Yasushi
Departments Of Neurosurgery Kyoto University Faculty Of Medicine
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ZHANG Xiao-Feng
Departments of Pharmacology, Kyoto University Faculty of Medicine
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ENOKI Taijiro
Departments of Anesthesiology, Kyoto University Faculty of Medicine
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OKAZAWA Makoto
Departments of Pharmacology, Kyoto University Faculty of Medicine
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Enoki Taijiro
Departments Of Anesthesiology Kyoto University Faculty Of Medicine
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Okazawa Makoto
Departments Of Pharmacology Kyoto University Faculty Of Medicine
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Zhang Xiao-feng
Departments Of Pharmacology Kyoto University Faculty Of Medicine
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Masaki Tomoh
National Cardiovascular Center Reseach Institute
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Miwa Soichi
Department Of Cellular Pharmacology Graduate School Of Medicine Hokkaido University
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