CaM Kinase II and the heart

[jan251]

Thanks to Rachel for pointing out the connection between the two - I wasn't aware.

 

http://circres.ahajournals.org/content/110/12/1661.full

 

Evidence assembled over the past decade supports a view that activation of the multifunctional Ca²⁺ and calmodulin-dependent protein kinase II (CaMKII) favors myocardial dysfunction and cell membrane electrical instability. CaMKII activation follows increases in intracellular Ca²⁺ or oxidation, upstream signals with the capacity to transition CaMKII into a Ca²⁺ and calmodulin-independent constitutively active enzyme. Constitutively active CaMKII appears poised to participate in disease pathways by catalyzing the phosphorylation of classes of protein targets important for excitation–contraction coupling and cell survival, including ion channels and Ca²⁺ homeostatic proteins, and transcription factors that drive hypertrophic and inflammatory gene expression. This rich diversity of downstream targets helps to explain the potential for CaMKII to simultaneously affect mechanical and electrical properties of heart muscle cells. Proof-of-concept studies from a growing number of investigators show that CaMKII inhibition is beneficial for improving myocardial performance and for reducing arrhythmias.

 

 

Does anyone's child have both a high CaM Kinase II and a heart issue?

 

(My son has both a genetic hypertrophic cardiomyopathy and an abnormal EKG, a delta wave similar to what is seen in WPW, but both were known well prior to the sudden onset of the OCD). So for me, the interesting part of the document is the following:

 

Taken together, we interpret these findings to suggest that a complex interplay between hypertrophic, inflammatory, and likely yet to be identified transcriptional pathways are activated directly or indirectly by CaMKII. The potential complexity of these interactions is highlighted by a recent study showing that the role of CaMKII to promote pathological hypertrophy appears to be antagonized by protein kinase A, a protein kinase that is responsive to cAMP and that is activated by catecholamines. Although mice with transgenic myocardial protein kinase A overexpression showed myocardial hypertrophy,¹³⁴ protein kinase A leads to an inhibitory CaMKII-insensitive cleavage product of HDAC4 that antagonizes hypertrophic actions of CaMKII.¹³⁵ Despite these complexities, we anticipate that the net effect of CaMKII in these pathways varies over time and differentially couples to upstream pathological stress signals; however, in the aggregate downstream CAMKII actions are maladaptive and so are candidate targets for future antiarrhythmic and anticardiomyopathic therapies.

 

 

A more important question: CaMKII can be inhibited?!

 

Dilated cardiomyopathy, exercise intolerance, and CaMKII activity in these mice were partially reversed by an angiotensin II receptor antagonist,⁴⁵ further suggesting that the success of angiotensin II antagonist drug therapy is at least partially attributable to CaMKII inhibition

 

 

Is the current theory that CaMKII is within the chain of causation, or merely correlated, with PANDAS? It's been a while since I read about it.

Edited January 3, 2015 by jan251

[911RN]

I would recommend CoQ10 if your child is not already taking it...leading cardiologists recommend it for patients with heart failure which is similar condition to hypertropic cardiomyopathy. It helps with the fatigue and improves endurance, exercise tolerance. Buy a quality Coq10 for better absorption. It's not cheap but not cost prohibitive either.

 

My son had very poor endurance and fatique, tired easily from minimal exertion. He takes SSRI now which is known to deplete CoQ10- however, he was like this before ever taking SSRI's. His energy level and endurance improved greatly with daily supplementation of CoQ10.

 

As for if the CamkIi can be inherited---that would be a question for Swedo, I suppose? IDK.

[kim]

Jan,

 

 

A more important question: CaMKII can be inhibited?!

 

??????

 

http://www.sciencedaily.com/releases/2008/05/080501125455.htm

Specifically, they showed that oxidation of two neighboring methionines -- sulfur-containing amino acids -- can sustain CaM kinase activity. Loss of these two methionines prevents activation by oxidation. They also found that they could return CaM kinase to its inactive state and inhibit heart cell death and dysfunction by using an enzyme called methionine sulfoxide reductase A (msrA), which reverses the methionine oxidation. Studies in worms, fruit flies and mice have shown that msrA increases lifespan, but, until now, the enzyme's targets in heart were unknown

 

http://www.jneurosci.org/content/27/47/12808.abstract

Methionine Sulfoxide Reductase A and a Dietary Supplement S-Methyl-L-Cysteine Prevent Parkinson's-Like Symptoms

Furthermore, we demonstrate that one way to enhance the MSRA antioxidant system is dietary supplementation with S-methyl-L-cysteine (SMLC), found abundantly in garlic, cabbage, and turnips. SMLC,

 

Is the current theory that CaMKII is within the chain of causation, or merely correlated, with PANDAS? It's been a while since I read about it.

 

 

I think a Dr. (lab) that measures CaMKII was supposed to have said that it was unknown what CaMKII levels looked like in nomal children with strep, so I'm going to venture a guess that it's more of a correlation at this point. I found it interesting to see the results of high CaMKII in kids that didn't have the classic overnight onset of symptoms too (the few that I knew of that didn't really identify with the PANDAS profile).

 

Something that stood out of something that you linked above

 

The potential complexity of these interactions is highlighted by a recent study showing that the role of CaMKII to promote pathological hypertrophy appears to be antagonized by protein kinase A, a protein kinase that is responsive to cAMP and that is activated by catecholamines. Although mice with transgenic myocardial protein kinase A

 

 

Read Buster's response here

 

http://latitudes.org/forums/index.php?showtopic=5683&page=3

 

He kind of lost me with the remark about cAMP which may tie in with what 911rn just posted regardiing COQ10 (effects on ATP)

 

from wiki on cAMP (just interesting)

 

http://en.wikipedia.org/wiki/Cyclic_adenosine_monophosphate
Role of cAMP in prefrontal cortex disorders

Recent research suggests that cAMP affects the function of higher-order thinking in the prefrontal cortex through its regulation of ion channels called hyperpolarization-activated cyclic nucleotide-gated channels (HCN). When cAMP stimulates the HCN, the channels open, closing the brain cell to communication and thus interfering with the function of the prefrontal cortex. This research, especially the cognitive deficits in age-related illnesses and ADHD, is of interest to researchers studying the brain.[6]

 

Edited February 27, 2015 by kim

[Rachel]

Cam Kinese can also affect NMDAR receptors and these receptors regulate glutamate. In the post I made earlier, I posted some of those articles. I will go back and recheck.

 

My son is diagnosised with Postural Orthostatic Tachycardia Syndrome. He tested positive for high Cam Kinese levels in 2013. He is under the care of a cardiologist and has been doing PEX treatments since last August. From what research I have read, Magnesium and NAC helps regulate glutamate and the NMDAR receptors. My son takes both of these supplements. His neurotransmitter glutamate levels were high but he has had the antibody test for celiac. The test was negative. So our doctor is thinking the high Cam Kinese is causing this problem. My son tried a gluten free and dairy free diet this last summer. It did not help any of his symptoms.

Edited January 3, 2015 by rachel