T3 intracellular calcium and caffeine

Iritu1021

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@Iritu1021 I was curious, does your new book list all of the meds that block the calcium channel?
It's about intracellular calcium, it doesn't go that much into calcium channels. I don't think he mentions anything beyond the usual calcium channel blockers.

But I found this one online (p.311-312) where it says that modulation of intracellular Ca leads to EBV genome activation through an effect on PKC.

I suspect the combination of Armour thyroid and stimulants caused the change in my intracellular calcium that activated my EBV and caused my CFS.

I'm starting to think that @debored13 might be right about Naviaux's CDR and that hypometabolic rate has a protective purpose, and if you push it beyond a certain threshold you end up paying a price for it sooner or later.

When I tried to push high NDT doses according to what STTM and other alternative blogs recommend, I ended up with extreme muscular weakness and ptosis which clinically resembled myasthenia gravis or Lamber Eaton. So I stopped all thyroid hormone cold turkey, made myself really hypothyroid and miserable but the muscle weakness and ptosis resolved on their own.
 

Gingergrrl

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It's about intracellular calcium, it doesn't go that much into calcium channels. I don't think he mentions anything beyond the usual calcium channel blockers.
Thanks and I was just curious.

When I tried to push high NDT doses according to what STTM and other alternative blogs recommend, I ended up with extreme muscular weakness and ptosis which clinically resembled myasthenia gravis or Lamber Eaton. So I stopped all thyroid hormone cold turkey, made myself really hypothyroid and miserable but the muscle weakness and ptosis resolved on their own.
Do you mean that you took a high dose of Armour (or some other NDT) and that alone caused you to have muscle weakness similar to MG or LEMS?! Did you also have breathing/diaphragm weakness like I did? Can you remind me if you have ever been tested for the N-type or P/Q-type CA+ Channel Autoantibodies?

I never had ptosis or any ocular issue. I also only took a very low dose of Armour (my dose ranges from 7.5 mg to 15 mg depending on my thyroid numbers) and I have never taken more than 15 mg per day.
 

pattismith

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Voltage gated sodium channels. You can't get it IV but you can approximate the effect by lidocaine oral spray or patches which you can buy online.
VGSC are important in the pain transduction.

.
Intravenous lidocaine is very effective for chronic and acute pain, so I have considered it, but oral ambroxol seems so much easier.

What amazes me is that these sodium channels blockers have both an immediate action on pain, and a delayed action on inflammation, and I need both....

I am also interested on Ambroxol because it was suggested it may have an effect on tinnitus.

The thing is it may not be a good association with T3, so I will see if I can stop it while on Ambroxol.
 

Inara

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What I'm learning right now is that the interplay of all these channels is extremely complex
Honestly, that helped. :D Via googlebooks I only could see snips. And yes, after having had a look at several papers: It is very complicated. Didn't know, yet, that voltage-gated calcium channels are (directly?) connected to IP3Rs (and RYRs). But these voltage-gated channels aren't on the ER?
 

Inara

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It is remarkable that many tricyclic antidepressants, selective serotonin-reuptake inhibitors, and serotonin–norepinephrine reuptake inhibitors also block sodium channels
They also act at other positions, and I wouldn't play with psychopharmaceuticals. They are too well-known for their side effects. And now that I am more aware of the complex interplay in the body, I wouldn't want to interrupt anything, especially nothing as central as sodium channels.
But the biochemistry behind it is interesting indeed.
 

Inara

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I have received a reply by an immunologist regarding the mutation that was found. They will test the calcium flux of the receptor (or all receptors??) - I didn't know that's possible in a clinical setting. But it's great - because it's important to know whether there's too much or too less flux, something I felt was not trivial (for me) to determine.
If there's interest, I can tell more when I know more.
 

debored13

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It's about intracellular calcium, it doesn't go that much into calcium channels. I don't think he mentions anything beyond the usual calcium channel blockers.

But I found this one online (p.311-312) where it says that modulation of intracellular Ca leads to EBV genome activation through an effect on PKC.

I suspect the combination of Armour thyroid and stimulants caused the change in my intracellular calcium that activated my EBV and caused my CFS.

I'm starting to think that @debored13 might be right about Naviaux's CDR and that hypometabolic rate has a protective purpose, and if you push it beyond a certain threshold you end up paying a price for it sooner or later.

When I tried to push high NDT doses according to what STTM and other alternative blogs recommend, I ended up with extreme muscular weakness and ptosis which clinically resembled myasthenia gravis or Lamber Eaton. So I stopped all thyroid hormone cold turkey, made myself really hypothyroid and miserable but the muscle weakness and ptosis resolved on their own.
Maybe Im right, maybe i'm wrong... I really was only speculating there. What I think is more certain is that this is true contingent on nutrition and other similar factors... Even if chronic viral/bacterial infections were still around in a large swathe of the patient population, which goes against what Davis and Naviaux say (but let's just say it's true, and maybe it is, i'm not trying to say either way), it's not necessarily true that the hypometabolic state would still be protective against them. I think there's a difference between saying something is adaptive and saying that it's inherently good/protective. Our adaptations could be maladaptive. So even if the virus or whatever trigger is still there, it could be at a very low level, and I don't see how raising metabolism is necessarily going to hurt. If we raise metabolic rate it may cause initial reactivation of viruses, because a rise in metabolism could reactivate a dormant immune system, so I could see initial symptoms that have to do with feeling fluish, etc, to rise.

Also, I'm not sayng treating viruses or bacteria isn't good, and I'm not trying to start an argument re: that. I just think that healthy people have a lot of the same viruses or bacteria as we do. The problem is more complex.

But maybe one thing isn't enough to bring us fully out of this hypometabolic state, given how steady it is, like a form of homeostasis (maybe should be called heterostasis?), and it requires a finely tuned cocktail of things that work together, given how complex metabolism is and how we might deplete nutrients over a period of illness.


Anyway, this is all untrained speculation
 

drob31

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Intravenous lidocaine is very effective for chronic and acute pain, so I have considered it, but oral ambroxol seems so much easier.

What amazes me is that these sodium channels blockers have both an immediate action on pain, and a delayed action on inflammation, and I need both....

I am also interested on Ambroxol because it was suggested it may have an effect on tinnitus.

The thing is it may not be a good association with T3, so I will see if I can stop it while on Ambroxol.

Can you tell me where you found ambroxol?
 

Iritu1021

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Thanks and I was just curious.



Do you mean that you took a high dose of Armour (or some other NDT) and that alone caused you to have muscle weakness similar to MG or LEMS?! Did you also have breathing/diaphragm weakness like I did? Can you remind me if you have ever been tested for the N-type or P/Q-type CA+ Channel Autoantibodies?

I never had ptosis or any ocular issue. I also only took a very low dose of Armour (my dose ranges from 7.5 mg to 15 mg depending on my thyroid numbers) and I have never taken more than 15 mg per day.
The weakness and ptosis happened when I tried to go over 2 grains of Armour. I also had exophthalmos (protruding eyeballs similar to Graves), severe facial swelling, and what felt like right-sided heart failure.

But I don't think I had diaphragmatic weakness. It was hard to breathe but I think it was due to the heart weakness rather than the diaphragm. Can't be sure - that time was such a blur, my brain wasn't working well either. But I do remember that my eyelids looked very droopy and that it became very difficult to even lift my arm.

I never even went to see any doctor - I couldn't get out of bed during that time and also because I knew that it was due to Armour and it did go away after I stopped it. But I still can't tell what the mechanism was.

Did you mention that you also got worse when your doctor tried to raise your Armour?
 

Iritu1021

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Intravenous lidocaine is very effective for chronic and acute pain, so I have considered it, but oral ambroxol seems so much easier.

What amazes me is that these sodium channels blockers have both an immediate action on pain, and a delayed action on inflammation, and I need both....

I am also interested on Ambroxol because it was suggested it may have an effect on tinnitus.

The thing is it may not be a good association with T3, so I will see if I can stop it while on Ambroxol.
What is the interaction with T3 - is it because they both act on sodium channels?

We have lidocaine creams and patches here. I just ordered some on Amazon, will try for my neck spasms.
 

Iritu1021

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Maybe Im right, maybe i'm wrong... I really was only speculating there. What I think is more certain is that this is true contingent on nutrition and other similar factors... Even if chronic viral/bacterial infections were still around in a large swathe of the patient population, which goes against what Davis and Naviaux say (but let's just say it's true, and maybe it is, i'm not trying to say either way), it's not necessarily true that the hypometabolic state would still be protective against them. I think there's a difference between saying something is adaptive and saying that it's inherently good/protective. Our adaptations could be maladaptive. So even if the virus or whatever trigger is still there, it could be at a very low level, and I don't see how raising metabolism is necessarily going to hurt. If we raise metabolic rate it may cause initial reactivation of viruses, because a rise in metabolism could reactivate a dormant immune system, so I could see initial symptoms that have to do with feeling fluish, etc, to rise.

Anyway, this is all untrained speculation
Well, at this point everybody's just speculating - not just us but all the experts too.

My personal experience is that I have a very narrow range of how much thyroid I can get away with.

But now this range seemed to have expanded after I went on lithium.

Lithium decreases PKC and EBV virus relies on PKC for activation so I might be using lithium orotate as an antiviral.
In the past, the level of thyroid I have right now would give me POTS but now it doesn't. It just makes me feel hyperthyroid, and while overall I'm better I noticed that my chronic throat pain (the primary area of EBV) is getting worse.

While everyone has viruses, I think there might be a difference in how the virus integrates itself into the genome, which might depend on the particular interplay of individual genetics and the particular strain of virus, etc.

For example, if EBV relies on calcium for replication, it might manipulate your genome and change the structure of your calcium channels to increase the calcium influx into the cell - good for the virus but bad for you. (If that's the case the antibodies against calcium channels might even be protective mechanism to downregulate Ca2+).
 

Iritu1021

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They also act at other positions, and I wouldn't play with psychopharmaceuticals. They are too well-known for their side effects. And now that I am more aware of the complex interplay in the body, I wouldn't want to interrupt anything, especially nothing as central as sodium channels.
But the biochemistry behind it is interesting indeed.
I can't tolerate any of this drugs. But lithium orotate (which is technically a supplement, not a drug) has done wonders for me. The initial effects were unpleasant and probably related to its effect on sodium channels, but the intracellular effects were really positive.
 

Iritu1021

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I have received a reply by an immunologist regarding the mutation that was found. They will test the calcium flux of the receptor (or all receptors??) - I didn't know that's possible in a clinical setting. But it's great - because it's important to know whether there's too much or too less flux, something I felt was not trivial (for me) to determine.
If there's interest, I can tell more when I know more.
That's great! Of course, there's interest - can't wait to hear the results! Should we start taking bets?;)
 

Iritu1021

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Honestly, that helped. :D Via googlebooks I only could see snips. And yes, after having had a look at several papers: It is very complicated. Didn't know, yet, that voltage-gated calcium channels are (directly?) connected to IP3Rs (and RYRs). But these voltage-gated channels aren't on the ER?
The voltage-gated channels are on the plasma membranes, they play a big role in membrane depolarization and neuronal impulse propagation.
The ER channels are more involved in regulating signal transduction between hormonal receptors and nucleus and in mitochondrial function.
But they do talk to each other to maintain a tight balance of calcium in the cytoplasm. Unless of course this communication somehow gets disrupted.

Came across this in the chapter on calcium and vision.

Dopamine, somatostatin, adenosine, glutamatate, insulin, GABA, retinoids, cannabinoids, H+, Cl- can modulate inner segment Ca2+ channels, acting as secondary regulators of glutamate.

I wish it would say how exactly they modulate it.

Also this:
Cadmium and cobalt can act as L-type Ca2+ channel blockers.

When my calcium was really high on hair analysis in 2014, my cadmium and cobalt were both elevated...
 
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Iritu1021

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Here's more from the book:

Eukaryotic viruses affect cell metabolism and can exploit, hijack, or disrupt the Ca2+ signaling system in order to take over the biochemistry of a cell, and replicate. Many viruses interfere with normal Ca2+ signaling, involving effects on Ca2+ channels int he plasma membrane, and Ca2+movement in the ER and mitochondria. Viruses can induce cytosolic free Ca2+ signals through SOCE, voltage-gated Ca channels, and metabotropic Ca2+ channels. They can also form ion channels and pores from viroporin proteins. Viruses can affect gene expression and replication through activation of Ca2+ calmodulin kinases (CaMKs) and calreticulin. The alteration in Ca2+ signaling either enhances viral replication or prevents the cell going into apoptosis, which would otherwise leave the virus stranded mid-stream. Intracellular Ca2+ also plays a crucial role in the immune system.

Herpes simplex activates a rapid cytosolic Ca 2+ transient through the production of IP3. This is necessary for the activation of focal adhesion kinase.

Similarly, coxsackievirus B activates phospholipase C (PLC) in endothelial cells, IP3 releasing Ca2+ from the ER, thereby activating SOCE.

Epstein-Barr virus immortalizes lymphocytes, altering Ca2+ signaling by increasing ER Ca2+, affecting the resting cytosolic free Ca2+ and SOCE. LMP-1 is a key EBV protein in this process, increasing SOCE through the expression of STIM and Orai. EBV also reduces the release of cytochrome c from mitochondria, by interfering with the voltage-dependent anion protein 2.

Infection of cells by cytomegalovirus causes a rise in cytosolic free Ca, having major effects om intermediary metabolism, including glycolysis, the citric acid cycle, fatty acid, and nucleotide synthesis.
 

Gingergrrl

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I have received a reply by an immunologist regarding the mutation that was found. They will test the calcium flux of the receptor (or all receptors??) - I didn't know that's possible in a clinical setting. But it's great - because it's important to know whether there's too much or too less flux, something I felt was not trivial (for me) to determine. If there's interest, I can tell more when I know more.
@Inara We are definitely interested and I hope you will post more info once you get it (but you will have to explain it to me in baby terms :nerd:).

The weakness and ptosis happened when I tried to go over 2 grains of Armour. I also had exophthalmos (protruding eyeballs similar to Graves), severe facial swelling, and what felt like right-sided heart failure.
It sounds like you (temporarily) ended up severely hyperthyroid from the high dose of Armour. I am still not sure why they call it "grains" but I Googled my dose of Armour and when I was on the lower dose it was 1/8 of a grain and at my higher (current) dose it is 1/4 of a grain which is 15 mg. If I'm understanding correctly, you were taking a dose 8x higher than mine!

Did you mention that you also got worse when your doctor tried to raise your Armour?
No, I actually do well with both doses (the 1/8 or the 1/4 grain) of Armour and they adjust it according to my TSH level and other numbers. But I have never taken a dose even remotely as high as what you had tried.

The voltage-gated channels are on the plasma membranes, they play a big role in membrane depolarization and neuronal impulse propagation.
How does that translate into functional terms? Would it affect things like muscle strength/weakness?
 

Iritu1021

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@Inara We are definitely interested and I hope you will post more info once you get it (but you will have to explain it to me in baby terms :nerd:).

It sounds like you (temporarily) ended up severely hyperthyroid from the high dose of Armour. I am still not sure why they call it "grains" but I Googled my dose of Armour and when I was on the lower dose it was 1/8 of a grain and at my higher (current) dose it is 1/4 of a grain which is 15 mg. If I'm understanding correctly, you were taking a dose 8x higher than mine!
I was not using it according to the instructions, that's for sure - but these are not typical symptoms of hyperthyroidism so I think it was due to something else that was triggered by hyperthyroidism but specific to mine body. I also developed POTS from just 1/2 grain of Armour. My endocrinologist at the time insisted that it was physically impossible to be made hyperthyroid by such a small dose.
 
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Iritu1021

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Intravenous lidocaine is very effective for chronic and acute pain, so I have considered it, but oral ambroxol seems so much easier.

What amazes me is that these sodium channels blockers have both an immediate action on pain, and a delayed action on inflammation, and I need both....

I am also interested on Ambroxol because it was suggested it may have an effect on tinnitus.

The thing is it may not be a good association with T3, so I will see if I can stop it while on Ambroxol.
@pattismith, I found this interesting article that talks about the thyroid effect on sensory perception and neuronal excitability.

https://www.intechopen.com/books/th...eed-neuronal-excitability-and-ion-channel-reg

"Concerning the action of thyroid hormone on neuronal excitability, there seems to be a common finding that the density of voltage-gated Na+currents is up-regulated by thyroid hormone rendering the cells more excitable".

So maybe just lowering or stopping T3 will be enough by itself to help with your pain. For me there definitely seems to be an association between my T3 levels and my central pain sensitization.
 

Iritu1021

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Vinpocetine is as potent as phenytoin to block voltage-gated Na+ channels in rat cortical neurons.
Molnár P1, Erdö SL.
Author information

Abstract
The effects of vinpocetine and phenytoin on voltage-gated Na+ channels were examined on cultured cerebrocortical neurones of the rat using a conventional whole-cell patch-clamp method. Vinpocetine and phenytoin decreased Na+ currents in a concentration-dependent manner, with IC50 values of 44.2 +/- 14.6 and 50.5 +/- 17.4 microM, respectively. Both compounds shifted the voltage dependence of the steady-state inactivation of the channel in the hyperpolarising direction. This pronounced Na+ channel blocking activity may contribute to the neuroprotective and anticonvulsant effects of vinpocetine.
 

Inara

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and when I was on the lower dose it was 1/8 of a grain and at my higher (current) dose it is 1/4 of a grain which is 15 mg. If I'm understanding correctly, you were taking a dose 8x higher than mine!
Woah! That is much! I take 2 x 2.5 micrograms T3 per day and ca. 90 micrograms T4 per day.
mg?!