long QT syndrome and genetics and potassium ion channels, o my

[news.sciencemag.org]

title: Heart Defect: Medicate or Wait?

excerpt: "Warning signs. In long QT syndrome, potassium channels (orange and blue) that open too slowly can lead to irregular heart rhythms."

Relation to afib: afibbers sometimes also have long QT syndrome, often leading to bad reactions to some common medications and to hurry-up installation of pacemakers. We hear from these persons fairly frequently here.

Also, even those afibbers who do not have long QT seem often to have some kind of difficulty in relation to potassium, judging from those who have found relief from afib by regulation of salt to potassium ratios or by simply increasing potassium intake to better match our government's RDA for potassium, 4700 mg each day for an adult.

Many persons eat the SAD diet, but comparatively few develop afib. Why is that? Further, afib, like long QT,seems to have something to do with inheritance, though it is very difficult to say just what is being inherited that leads whole families to develop afib.

I think it will require somebody like Erling or the long-vanished PC to puzzle this out for us here. Certainly i am not equal to this task.



PeggyM

further quote, expressing a most poignant sentiment: ""Doctors want to know the risk of dropping dead tomorrow. That's really the quagmire in this field," says human geneticist Alfred George of Vanderbilt University in Nashville. "

Me too, dear doctor, can you tell me that please?

PeggyM

There are a number of really good artricles on LQTS Syndrome published by the Cleveland Clinic.

Here's the Google directory list:
[www.google.com]

My neighbor worked for CCF physician whose son died suddenly at age 12 from LQTS...so the papers were full of information about how to check for the genetics, etc.

Clip from the first reference
[my.clevelandclinic.org]

What is LQTS?

Long Q-T syndrome is a disorder of the heart’s electrical system.

The electrical activity of the heart is produced by the flow of ions (electrically charged particles of sodium, calcium, potassium, and chloride) in and out of the cells of the heart. Tiny ion channels control this flow.

The Q-T interval is the section on the electrocardiogram (ECG) - that represents the time it takes for the electrical system to fire an impulse through the ventricles and then recharge. It is translated to the time it takes for the heart muscle to contract and then recover.

LQTS occurs as the result of a defect in the ion channels, causing a delay in the time it takes for the electrical system to recharge after each heartbeat.

When the Q-T interval is longer than normal, it increases the risk for torsade de pointes, a life-threatening form of ventricular tachycardia.

LQTS is rare. The prevalence is about 1 in 5,000 persons in the Untied States.

Hm. First time I've seen it called that.

Though one witty Canadian journalist called it the Excited States.

Peggy,

Here is a basic explanation of the heart beat.

[www.afibbers.org]

Hans

Thank you, Hans, for that nice clear simple explanation. It is as good as one i might have found in the old World Book, before the internet.

I am curious why you thought i needed this particular explanation at this particular time. Did any of the questions i asked in my post seem to you to show some basic flaw in my admittedly minor knowledge about the heart?

The only direct question i asked was this one: "Many persons eat the SAD diet, but comparatively few develop afib. Why is that? "

Was that the one that prompted you to explain the basic workings of the heart to me? Or was it the implied question about how come posters here so often have several close relatives with afib also? Was it that i wished for PC or Erling to puzzle out the relation, if any, between long QT syndrome, sudden cardiac death, and the rest of us afibbers? Does this explanation answer any of those, and i am just too dense to see the relationship? Anyone may jump in here and answer, please.

The old ignoramus

PeggyM

Peggy

'Old ignoramus' you certainly are not - I have learned a great deal from you, and I am sure that others have too. You have a way of getting to the nub of things while keeping everything simple and straightforward.

I would guess that Hans incuded that basic explanation for other people reading the thread who might not know as much as you.

Gill

Peggy - in the CCF explanation, it indicates that LQTS can be the result of genetics or is acquired and goes on to explain. In the case I mentioned, it was traced to maternal genes.

In the report on Magnesium Absorption and in the notes by Dr. Burford-Mason, she said several genenetic defects had been identified and that probably more would be discovered. Remember, it's not so much that you have the genetic tendency, it's how one's lifestyle and environment affect the genetic EXPRESSION. There are many ways to dampen or discourage the expression of gene flaws.

Jackie

Gill,

Exactly! I certainly did not mean to imply that Peggy needed a basic lesson on the heart's workings; however other posters might be interested.

Hans

Hi Peggy,

Your insightful questions were inspired by the insightful article Heart Defect: Medicate or Wait? (http://news.sciencemag.org/sciencenow/2011/03/heart-defect-medicate-or-wait.html?ref=hp)

Pithy excerpt: (not a lisp)

"Biophysicist Coeli Lopes and colleagues at the University of Rochester Medical Center in New York wanted to find out what these mutations actually do. They focused on a gene linked to more than 50% of long QT syndrome cases that codes for a protein called KCNQ1, which is part of [??] a potassium channel. Working with collaborators in Japan, Denmark, and the Netherlands, they gathered medical records for 387 patients from families with long QT syndrome who carried one copy of 17 common mutations in the KCNQ1 gene.

The researchers engineered frog eggs to express the 17 abnormal forms of KCNQ1, then measured how the cells transmitted electrical currents. Certain mutations made the potassium channels carry less current and open more slowly than normal channels. When Lopes's group checked the patients' medical histories, the researchers found that those with slowly activating channels were two times more likely than patients with other mutations to die before age 30 or develop serious symptoms such as fainting spells or heart attacks."

I thought to leave it at "o my", but somehow wound up deep in Wikipedia and Wiktionary where 4 years could earn one a PhD for sure. Everything one might want to know about building a potassium channel, and more:

[en.wikipedia.org]
[en.wikipedia.org]
[en.wikipedia.org]
<[en.wikipedia.org];
[en.wiktionary.org]

... which led to:

The KCNQ1 Potassium Channel: From Gene to Physiological Function 2005 Int. Union Physiol. Sci./Am. Physiol. Soc.
[physiologyonline.physiology.org], or [physiologyonline.physiology.org]
Thomas Jespersen, Morten Grunnet, and Soren-Peter Olesen
Department of Medical Physiology and Danish Arrhythmia Research Center,
The Panum Institute, University of Copenhagen, Copenhagen, Denmark, and NeuroSearch, Ballerup, Denmark

... and here's where it got rich:

Cardiac Mitochondria and Arrhythmias Cardiovascular Research Advance Access published July 9, 2010
[cardiovascres.oxfordjournals.org]
David A. Brown1 and Brian O'Rourke2
1 Department of Physiology, Brody School of Medicine and the East Carolina Heart Institute, East Carolina University, Greenville NC USA
2 Department of Cardiology, The Johns Hopkins School of Medicine, Baltimore MD USA

Pithy quote:

"Sarcolemmal ion channel mutations leading to prolongation of the action potential (i.e. long QT syndrome), early- or delayed after-depolarizations due to activation of calcium channels/exchangers, and altered transsarcolemmal ion gradients have all been extensively described in their arrhythmogenic role7. In this article we will discuss the role that cardiac mitochondria play in influencing cardiomyocyte action potential duration, underscoring therapeutic potential for arrhythmia using mitochondria-targeted approaches."

Pithy thoughts:

-- Genes do not directly code for proteins. Why? - there aren't nearly enough nuclear genes to code for the vastly larger number of proteins comprising the human body. Enter 'epigenetics' ('above genetics') where ultimate 'gene expression' occurs (see Introduction to 'epigenetics' and 'methylation' (http://www.afibbers.org/forum/read.php?f=8&i=24804&t=24804).

-- In The Biology of Belief quantum cell biologist Dr. Bruce Lipton makes it clear that we are not victims of our genes - unless we believe we are - because proteins may be modified by information from the cell's outer membrane - the cell/computer's keyboard equivalent. The cell's outer membrane is exquisitely sensitive to its environmental fields, which extend beyond physical substances in the extracellular fluid to include electromagnetic fields and thought (witness placebo/nocebo effects, and 'psychic' healers such as Edgar Cayce (http://en.wikipedia.org/wiki/Edgar_Cayce)

-- The cell is governed by electronics/electricity. KCNQ1 is a 'voltage gated' potassium channel. Even if perfectly configured it still requires optimal voltage to open optimally, therefor Long Q-T can be caused by inhibited functioning of voltage-generating Na/K pumps, which are driven by ATP produced by the mitochondria, which require proper nourishment of the Krebs/aka citric acid/aka tricarboxylic acid cycle in the mitochondrial inner 'matrix': [www.wiley.com].

-- which makes one wonder about the vast number of 20 different amino acids required for proper form / function of KCNQ1. We haven't focused enough on 'channelopathies' resulting from dietary or internally-synthesized amino acid shortfalls (http://en.wikipedia.org/wiki/Channelopathy).

-- which takes us back to a dietary potassium:sodium ratio of at least 4:1 for optimal cell voltage.

-- which takes us back to the paleolithic diet and a K:Na ratio greater than 12:1 (<[www.afibbers.org]. Which makes one wonder if cave men/ladies suffered from long cuties? Unfortunately their medical records have not been discovered. . .

o my. . .

Erling

PS - relevant pithy quotes:

2001, Biophysist Dr. Richard Moore in The Salt Solution p. 192, ref. 28:

"Only scientists who have spent their lives looking at these systems [the living cell] can truly appreciate what a fantastically interconnected system the cell actually is. A spider's web would be the best analogy I can think of, and a poor one at that. If you touch one part of the web, every other part moves also. But whereas the spider's web is a two-dimensional network, the living cell is a multidimensional network. Where the different regions of a spider's web move a bit when one part is touched, different regions of the living cell can go though whole transformations as a result of an initial change in just one particular part. The cell is a miraculously complex phenomenon indeed!"

2005, Cell biologist Dr. Bruce Lipton in The Biology of Belief pp. 72 - 74:

"Cellular constituents are woven into a complex web of crosstalk, feedback and feedforward communication loops. A biological dysfuntion may arise from a miscommunication along any of the routs of communication flow. To adjust the chemistry of this complicated interactive system requires a lot more understanding than just adjusting one of the information pathway's components with a drug. . . Newtonian research scientists have not fully appreciated the extensive interconnectivity among the cell's biological information networks."

Erling - Interesting input. Lots to read and consider. I like pithy.

-- which makes one wonder about the vast number of 20 different amino acids required for proper form / function of KCNQ1. We haven't focused enough on 'channelopathies' resulting from dietary or internally-synthesized amino acid shortfalls (http://en.wikipedia.org/wiki/Channelopathy).

On this segment...have you uncovered a scale or guideline that indicates the appropriate amount of amino acid/protein intake we should have to ensure there is enough for this function?

Jackie

Jackie - a good place for answers to your query, "have you uncovered a scale or guideline that indicates the appropriate amount of amino acid/protein intake we should have to ensure there is enough for this function?" is Dr. Eric Braverman's et al 'The Healing Nutrients Within' beginning on p. 4, 'Dietary Requirements for Amino Acids', which leads to 'The Much Maligned Egg: The Best Amino Acid Food' (p. 7) and 'The Optimal Amino Acid Diet' on p.8.
(book, reviews, and 'look inside' are at [www.amazon.com])

I've only been 'at' this language of yours for some 70 years (the first 4 in California don't count) and always figured funny sounding 'pithy' was not for polite company - until just now discovering that it actually means good things like succinct, concise, and meaningful, so I 'ran it up the flagpole' and you saluted! - thanks!

Erling

Musings on Peggy's musings:

"Relation to afib: afibbers sometimes also have long QT syndrome, often leading to bad reactions to some common medications and to hurry-up installation of pacemakers. We hear from these persons fairly frequently here."

-- A lengthened Q-T interval will shorten the cells' 'refractory period' (RP), but if the billions (literally) of cells' RPs overlap enough (i.e. minimal "dispersion of refractoriness"-- thanks PC) normal rhythm may still be maintained - or maybe not: a common medication or supplement might be 'the last straw'. An artificial pacemaker is to protect against potentially lethal ventricular arrhythmia.

"Also, even those afibbers who do not have long QT seem often to have some kind of difficulty in relation to potassium, judging from those who have found relief from afib by regulation of salt to potassium ratios or by simply increasing potassium intake to better match our government's RDA for potassium, 4700 mg each day for an adult."

-- Hmm. The US Institute of Medicine determined the 'Adequate Intake' (AI) for potassium for "healthy adults" to be "at least" 4700 mg/day. It would seem that very few people will 'naturally' take in that much K since it generally requires new awareness (a 'paradigm shift') along with paying unaccustomed attention to what is eaten and supplemented. As biophysics researcher Jerry Tennant, MD says in 'Healing is Voltage', the body - and heart - are controlled by electronics (electricity). As the K/Na ratio goes, so goes the cells' voltage, and quite possibly normal rhythm. But normal voltage is also needed for protein assembly and form/ function. It seems much to narrow to ascribe long Q-T segment only to genetics.

"Many persons eat the SAD diet, but comparatively few develop afib. Why is that? Further, afib, like long QT, seems to have something to do with inheritance, though it is very difficult to say just what is being inherited that leads whole families to develop afib."

-- Like Moore's three-dimensional spiderweb and Lipton's "complex web of crosstalk, feedback and feedforward communication loops", there are just too many variables for succinct, concise, meaningful understanding. Add to that the potential for malformed membrane ion receptors/effectors channels and pumps (Integral Membrane Proteins- IMPs) resulting from diet, let alone genetics, and the ball o' wax becomes a ball of yarn defying unraveling. For example, take a look at the complexity of the KCNQ1 protein and the discovered mutuations (Figure 1. Frequency and location of 74 different mutations in the KCNQ1 potassium channel) about 1/3rd down: Clinical Aspects of Type-1 Long-QT Syndrome by Location, Coding Type, and Biophysical Function of Mutations Involving the KCNQ1 Gene (http://circ.ahajournals.org/content/115/19/2481.full), also see the upper-left diagram at The Neuronal Channelopathies (http://brain.oxfordjournals.org/content/125/6/1177/F1.expansion) showing a potassium ion channel protein looped in-and-out and embedded within the cell membrane, where each individual circle (many hundreds) represents a single amino acid in precisely linked individual order. Not in a billion years will this design work, I'd say, there are just way too many ways for it to fail! Mother Nature is so incredibly smart.

May the volts be with you!

Erling

PS -

Dr. Richard Moore, The Salt Solution, p. 151, illustrating large intracellular effect from small decrease in cell membrane voltage:

"The level of sodium inside skeletal muscle cells ... was indeed found to be increased by 40% and the voltage of their membranes was decreased by [only] 3% ..."

(ref. 46:
"Increased electrogenic pumping and elevated sodium activity in skeletal muscle cells of hypertensive stroke-prone rats", G. D. Goggins and G. D. Webb, 'The Physiologist' 29 (1986): 129;
G. D. Goggins, "Intracellular sodium activity and membrane potential in skeletal muscle cells of spontaneously hypertebsive strokr-prone rarts")