当前位置： SCI文献检索 > CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY期刊下所有文献 > CaMKIIδ and cardiomyocyte Ca(2+) signalling new perspectives on splice variant targeting.

CaMKIIδ and cardiomyocyte Ca(2+) signalling new perspectives on splice variant targeting.

Abstract：

:Control of cardiomyocyte cytosolic Ca(2+) levels is crucial in determining inotropic status and ischemia/reperfusion stress response. Responsive to fluctuations in cellular Ca(2+), Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine kinase integral to the processes regulating cardiomyocyte Ca(2+) channels/transporters. CaMKII is primarily expressed either in the δB or δC splice variant forms, which may mediate differential influences on cardiomyocyte function and pathological response mechanisms. Increases in myocyte Ca(2+) levels promote the binding of a Ca(2+)/calmodulin complex to CaMKII, to activate the kinase. Activity is also maintained through a series of post-translational modifications within a critical region of the regulatory domain of the protein. Recent data indicate that the post-translational modification status of CaMKIIδB/δC variants may have an important influence on reperfusion outcomes. This study provided the first evidence that the specific type of CaMKII post-translational modification has a role in determining target selectivity of downstream Ca(2+) transporters. The study was also able to demonstrate that the phosphorylated form of CaMKII closely co-localizes with CaMKIIδB in the nuclear/myofilament fraction, contrasting with a co-enrichment of oxidized CaMKII in the membrane fraction with CaMKIIδC . It has also been possible to conclude that a hyper-phosphorylation of CaMKII (Thr287) in reperfused hearts represents a hyper-activation of the CaMKIIδB , which exerts anti-arrhythmic actions through an enhanced capacity to selectively increase sarcoplasmic reticulum Ca(2+) uptake and maintain cytosolic Ca(2+) levels. This suggests that suppression of global CaMKIIδ may not be an efficacious approach to developing optimal pharmacological interventions for the vulnerable heart.

journal_name

Clin Exp Pharmacol Physiol

journal_title

Clinical and experimental pharmacology & physiology

authors

Bell JR,Raaijmakers AJ,Janssens JV,Delbridge LM

doi

10.1111/1440-1681.12489

subject

Has Abstract

pub_date

2015-12-01 00:00:00

pages

1327-32

issue

eissn

0305-1870

issn

1440-1681

journal_volume

pub_type

杂志文章,评审

在线工具

CaMKIIδ and cardiomyocyte Ca(2+) signalling new perspectives on splice variant targeting.