Calmodulin Kinase II Is Involved in Voltage-dependent Facilitation of the L-type Cav1.2 Calcium Channel

Abstract

. Fifteen putative calmodulin kinase II phosphorylation sites were identified mostly in the carboxyl-terminal tail of Ca v 1.2. Neither truncation at amino acid 1728 nor changing the II-III loop serines 808 and 888 to alanines affected facilitation of the calcium current. In contrast, facilitation was decreased by the single mutations S1512A and S1570A and abolished by the double mutation S1512A/S1570A. These serines flank the carboxyl-terminal EF-hand motif. Immunoprecipitation of calmodulin kinase II with the Ca v 1.2 channel was not affected by the mutation S1512A/S1570A. The phosphorylation of the Ca v 1.2 protein was strongly decreased in the S1512A/S1570A double mutant. These results suggest that voltagedependent facilitation of the Ca v 1.2 channel depends on the phosphorylation of Ser 1512

Myoscape controls cardiac calcium cycling and contractility via regulation of L-type calcium channel surface expression

“…Cardiomyocytes from Myoscape KO mice still showed proper VDI and no relevant alterations of CDF, suggesting that Ca-calmodulin-dependent LTCC regulation is unaltered. This was further underlined by the finding that Myoscape did not differentially affect CamKII-dependent phosphorylation of the distal-C-terminus (DCT) at S1512, which mediates calcium current facilitation in the murine heart4143.…”

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

“…Erxleben et al (26) have reported that CaMKII phosphorylates Ser439 in the I-II loop (which contains a CaM-binding site) and Ser1517 (Ser1516 in guinea pig), thereby promoting mode 2 activity in the rabbit cardiac Cav1.2 channel. Lee et al have also reported that CaMKII phosphorylates Ser1512 and Ser1570 (Ser1517 / Ser1516 and Ser1575 / Ser1574 in rabbit / guinea-pig cardiac type) in the C-terminal tail of the rabbit smooth muscle Cav1.2 channel and thereby promotes voltage-dependent facilitation (34). Further studies should be done to clarify which site is responsible for the maintenance of the basal activity and can argument the binding of CaM to Ca 2+ channels.…”

“…Hudmon et al (33) have confirmed that the pore-forming α 1C subunit (Cav1.2) is a CaMKII substrate and that the interaction between CaMKII and the C-terminal of α 1C is essential for CDF of L-type channels. Voltage-dependent facilitation of the Ca 2+ current has also been attributed to CaMKII activation (34).…”

Erbin Enhances Voltage-Dependent Facilitation of Cav1.3 Ca2+Channels through Relief of an Autoinhibitory Domain in the Cav1.3 α1Subunit

“…For Ca v 1.2 L-type channels, various mechanisms for facilitation have been characterized, including those involving phosphorylation of the channel by cAMP-dependent protein kinase (PKA) (Catterall, 2000) and association with calmodulin-dependent protein kinase II (CaMKII) (Dzhura et al, 2000;Hudmon et al, 2005;Grueter et al, 2006;Lee et al, 2006). Although PKA and CaMKII also cause facilitation of Ca v 1.3 channels (Qu et al, 2005;Gao et al, 2006), the enhanced facilitation caused by erbin and splice variation of the ␣ 1 1.3 CT in our study differs from these mechanisms in a number of ways.…”