PubMed 20019447

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Cav1.2

Title: The distinct roles of calmodulin and calmodulin kinase II in the reversal of run-down of L-type Ca(2+) channels in guinea-pig ventricular myocytes.

Authors: Li-Ying Hao, Wu-yang Wang, Etsuko Minobe, Dong-yun Han, Jian-Jun Xu, Asako Kameyama, Masaki Kameyama

Journal, date & volume: J. Pharmacol. Sci., 2009 Dec , 111, 416-25

PubMed link:

In this study, we investigated the roles of calmodulin kinase II (CaMKII) and calmodulin (CaM) in the reversal of run-down of L-type Ca(2+) channels. Single Ca(2+)-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 muM CaMKII mutant T286D (CaMKIIT286D), a constitutively active type of CaMKII, induced the Ca(2+)-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 Ca(2+) channels.