2009年12月
The Distinct Roles of Calmodulin and Calmodulin Kinase II in the Reversal of Run-Down of L-Type Ca2+ Channels in Guinea-Pig Ventricular Myocytes
JOURNAL OF PHARMACOLOGICAL SCIENCES
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- 巻
- 111
- 号
- 4
- 開始ページ
- 416
- 終了ページ
- 425
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1254/jphs.09094FP
- 出版者・発行元
- JAPANESE PHARMACOLOGICAL SOC
In this study, we investigated the roles of calmodulin kinase II (CaMKII) and calmodulin (CaM) in the reversal of run-down of L-type Ca2+ channels. Single Ca2+-channel activities in guinea-pig ventricular myocytes were recorded using the patch-clamp technique, and run-down of the channel activities was induced by inside-out patch formation in the basic internal solution. At 1 min after patch excision, 1-30 mu M CaMKII mutant T286D (CaMKIIT286D), a constitutively active type of CaMKII, induced the Ca2+-channel activities to only 2%-10% of that recorded in the cell-attached mode. However, in the presence of CaMKIIT286D, the time-dependent attenuation of CaM's effects in the reversal of run-down was abolished. A GST-fusion protein containing amino acids 1509-1789 of the C-terminal region of guinea-pig Cav1.2 (CT1) was prepared. In pull-down assays, CT1 treated with CaMKIIT286D showed a higher affinity for CaM compared with CT1 treated with phosphatase. We propose a model in which CaMKII-mediated phosphorylation of the channels regulates the binding of CaM to the channels in the reversal of run-down of L-type Ca2+ channels.
- リンク情報
- ID情報
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- DOI : 10.1254/jphs.09094FP
- ISSN : 1347-8613
- Web of Science ID : WOS:000273203000010