Late Na(+) current (I(NaL)) and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) are both increased in the diseased heart. Recently, CaMKII was found to phosphorylate the Na(+) channel 1.5 (Na(v)1.5), resulting in enhanced I(NaL). Conversely, an increase of I(NaL) would be expected to cause elevation of intracellular Ca(2+) and activation of CaMKII. However, a relationship between enhance...

Calcium/calmodulin-dependent protein kinase II (CaMKII) is the main CaMK in skeletal muscle and its expression increases with endurance training. Because CaMKII has been implicated as a regulator of mitochondrial biogenesis and calcium handling, we investigated the effects of acute CaMKII overexpression in skeletal muscle in vivo. We overexpressed α/β-CaMKII in adult rat m. gastrocnemius (GM) a...

Wnt ligands working through Frizzled receptors have a differential ability to stimulate release of intracellular calcium (Ca(2+)) and activation of protein kinase C (PKC). Since targets of this Ca(2+) release could play a role in Wnt signaling, we first tested the hypothesis that Ca(2+)/calmodulin-dependent protein kinase II (CamKII) is activated by some Wnt and Frizzled homologs. We report tha...

NMDA treatment of cultured hippocampal neurons causes recruitment of CYLD, as well as CaMKII, to the postsynaptic density (PSD), as shown by immunoelectron microscopy. Recruitment of CYLD, a deubiquitinase specific for K63-linked polyubiquitins, is blocked by pre-treatment with tatCN21, a CaMKII inhibitor, at a concentration that inhibits the translocation of CaMKII to the PSD. Furthermore, CaM...

Calcium/calmodulin-dependent protein kinase II (CaMKII) has been described as a biochemical switch that is turned on by increases in intracellular calcium to mediate synaptic plasticity. Here, we show that reductions in CaMKII activity trigger persistent increases in intrinsic excitability. In spontaneously firing vestibular nucleus neurons, CaMKII activity is near maximal, and blockade of CaMK...

BACKGROUND Considerable evidence suggests that calcium/calmodulin-dependent protein kinase II (CaMKII) overactivity plays a crucial role in the pathophysiology of heart failure (HF), a condition characterized by excessive β-adrenoceptor (β-AR) stimulation. Recent studies indicate a significant cross talk between β-AR signaling and CaMKII activation presenting CaMKII as a possible downstream med...

Rationale: Differential effects of B and C subtypes of Ca /calmodulin-dependent protein kinase (CaMKII) on cardiomyocyte Ca handling and survival have been suggested to result from their respective nuclear versus cytosolic localizations. CaMKII subtype localization and its relationship to enzyme activation and target phosphorylation have not, however, been systematically evaluated. Objective: T...

alpha1-Adrenoceptor stimulation (alpha1ARS) modulates cardiac muscle contraction under physiological conditions by means of changes in Ca2+ current through L-type channels (ICa,L) and Ca2+ sensitivity of the myofilaments. However, the cellular mechanisms of alpha1ARS are not fully clarified. In this study, we investigated the role of Ca2+/calmodulin-dependent PK II (CaMKII) in the regulation of...

to the catalytic sites in the basal state. The binding of Ca 2ϩ /calmodulin releases this autoinhibition, allowing phosphorylation to take place at a critical threonine resi-a property that endows CaMKII with the ability Summary to decode Ca 2ϩ signals in a frequency-dependent man-We show that ␣ and ␤CaMKII are inversely regulated Schulman et al., 1992; see also Eshete and Fields, 2001). by act...

The gene for the alpha isoform of Ca2+/calmodulin-dependent kinase II (alpha CaMKII) codes for a multifunctional protein kinase that is found exclusively in the brain. Here we show that in skeletal muscle, an alternative nonkinase product, hereafter referred to as alpha KAP (alpha CaMKII association protein), is expressed from the same gene. alpha KAP consists of a C-terminal region that is ide...