Calmodulin- and Ca2+-Dependent Facilitation and Inactivation of the CaV 1.2 Ca2+ Channels in Guinea-Pig Ventricular Myocytes
The L-type Ca2+ channel (Ca V 1.2) shows clear Ca2+-dependent facilitation and inactivation. Here we have examined the effects of calmodulin (CaM) and Ca2+ on Ca2+ channel in guinea-pig ventricular myocytes in the inside-out patch mode, where rundown of the channels was controlled. At a free [Ca2+]...
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| Format: | Article |
| Language: | English |
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Elsevier
2010-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319309995 |
| _version_ | 1811266053578162176 |
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| author | Dong-Yun Han Etsuko Minobe Wu-Yang Wang Feng Guo Jian-Jun Xu Li-Ying Hao Masaki Kameyama |
| author_facet | Dong-Yun Han Etsuko Minobe Wu-Yang Wang Feng Guo Jian-Jun Xu Li-Ying Hao Masaki Kameyama |
| author_sort | Dong-Yun Han |
| collection | DOAJ |
| description | The L-type Ca2+ channel (Ca V 1.2) shows clear Ca2+-dependent facilitation and inactivation. Here we have examined the effects of calmodulin (CaM) and Ca2+ on Ca2+ channel in guinea-pig ventricular myocytes in the inside-out patch mode, where rundown of the channels was controlled. At a free [Ca2+] of 0.1 μM, CaM (0.15, 0.7, 1.4, 2.1, 3.5, and 7.0 μM) + ATP (2.4 mM) induced channel activities of 27%, 98%, 142%, 222%, 65%, and 20% relative to the control activity, respectively, showing a bell-shaped relationship. Similar results were observed at a free [Ca2+] <0.01 μM or with a Ca2+-insensitive mutant, CaM1234, suggesting that apoCaM may induce facilitation and inactivation of the channel activity. The bell-shaped curve of CaM was shifted to the lower concentration side with increasing [Ca2+]. A simple model for CaM- and Ca2+-dependent modulations of the channel activity, which involves two CaM-binding sites, was proposed. We suggest that both apoCaM and Ca2+/CaM can induce facilitation and inactivation of Ca V 1.2 Ca2+ channels and that the basic role of Ca2+ is to accelerate CaM-dependent facilitation and inactivation. Keywords:: calmodulin, Ca2+, cardiac myocyte, calcium channel |
| first_indexed | 2024-04-12T20:35:07Z |
| format | Article |
| id | doaj.art-9742e5767dff4ab78135ee3d4bf1508e |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-04-12T20:35:07Z |
| publishDate | 2010-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-9742e5767dff4ab78135ee3d4bf1508e2022-12-22T03:17:36ZengElsevierJournal of Pharmacological Sciences1347-86132010-01-011123310319Calmodulin- and Ca2+-Dependent Facilitation and Inactivation of the CaV 1.2 Ca2+ Channels in Guinea-Pig Ventricular MyocytesDong-Yun Han0Etsuko Minobe1Wu-Yang Wang2Feng Guo3Jian-Jun Xu4Li-Ying Hao5Masaki Kameyama6School of Pharmaceutical Science, China Medical University, Shenyang 110001, China; Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan; Department of Pharmacology, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, JapanDepartment of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, JapanSchool of Pharmaceutical Science, China Medical University, Shenyang 110001, China; Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, JapanDepartment of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, JapanSchool of Pharmaceutical Science, China Medical University, Shenyang 110001, China; Corresponding authors. *alyhao@mail.cmu.edu.cn, *bkame@m.kufm.kagoshima-u.ac.jpDepartment of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan; Corresponding authors. *alyhao@mail.cmu.edu.cn, *bkame@m.kufm.kagoshima-u.ac.jpThe L-type Ca2+ channel (Ca V 1.2) shows clear Ca2+-dependent facilitation and inactivation. Here we have examined the effects of calmodulin (CaM) and Ca2+ on Ca2+ channel in guinea-pig ventricular myocytes in the inside-out patch mode, where rundown of the channels was controlled. At a free [Ca2+] of 0.1 μM, CaM (0.15, 0.7, 1.4, 2.1, 3.5, and 7.0 μM) + ATP (2.4 mM) induced channel activities of 27%, 98%, 142%, 222%, 65%, and 20% relative to the control activity, respectively, showing a bell-shaped relationship. Similar results were observed at a free [Ca2+] <0.01 μM or with a Ca2+-insensitive mutant, CaM1234, suggesting that apoCaM may induce facilitation and inactivation of the channel activity. The bell-shaped curve of CaM was shifted to the lower concentration side with increasing [Ca2+]. A simple model for CaM- and Ca2+-dependent modulations of the channel activity, which involves two CaM-binding sites, was proposed. We suggest that both apoCaM and Ca2+/CaM can induce facilitation and inactivation of Ca V 1.2 Ca2+ channels and that the basic role of Ca2+ is to accelerate CaM-dependent facilitation and inactivation. Keywords:: calmodulin, Ca2+, cardiac myocyte, calcium channelhttp://www.sciencedirect.com/science/article/pii/S1347861319309995 |
| spellingShingle | Dong-Yun Han Etsuko Minobe Wu-Yang Wang Feng Guo Jian-Jun Xu Li-Ying Hao Masaki Kameyama Calmodulin- and Ca2+-Dependent Facilitation and Inactivation of the CaV 1.2 Ca2+ Channels in Guinea-Pig Ventricular Myocytes Journal of Pharmacological Sciences |
| title | Calmodulin- and Ca2+-Dependent Facilitation and Inactivation of the CaV 1.2 Ca2+ Channels in Guinea-Pig Ventricular Myocytes |
| title_full | Calmodulin- and Ca2+-Dependent Facilitation and Inactivation of the CaV 1.2 Ca2+ Channels in Guinea-Pig Ventricular Myocytes |
| title_fullStr | Calmodulin- and Ca2+-Dependent Facilitation and Inactivation of the CaV 1.2 Ca2+ Channels in Guinea-Pig Ventricular Myocytes |
| title_full_unstemmed | Calmodulin- and Ca2+-Dependent Facilitation and Inactivation of the CaV 1.2 Ca2+ Channels in Guinea-Pig Ventricular Myocytes |
| title_short | Calmodulin- and Ca2+-Dependent Facilitation and Inactivation of the CaV 1.2 Ca2+ Channels in Guinea-Pig Ventricular Myocytes |
| title_sort | calmodulin and ca2 dependent facilitation and inactivation of the cav 1 2 ca2 channels in guinea pig ventricular myocytes |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319309995 |
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