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T3 intracellular calcium and caffeine

Discussion in 'Other Health News and Research' started by pattismith, Jun 3, 2018.

  1. pattismith

    pattismith Senior Member

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    3,5,3′-Triiodothyronine deprivation affects phenotype and intracellular [Ca2+]i of human cardiomyocytes in culture

    2001

    Abstract

    Objective: A decrease in plasma T3 concentration is a frequent finding in patients with heart failure. However, the role of this ‘low T3 syndrome’ on disease evolution has never been clarified. As phenotypic and functional cardiomyocyte impairments are alterations that correlate with the failing myocardium, we studied the long-term effects of T3 deprivation on human cardiomyocyte structure and calcium handling.

    Methods:
    Atrial cardiomyocytes and myocardial tissue were cultured with or without 3 nM T3. Microscopical examination of structural features was followed by analysis of α-sarcomeric actinin and sarcoplasmic reticulum calcium ATP-ase (SERCA-2) content. Calcium handling was studied by [Ca2+]i imaging.

    Results:
    When stimulated with cyclopiazonic acid, a SERCA-2 inhibitor, T3-deprived cardiomyocytes showed significantly faster (P=0.03) and more transient (P=0.04) increases in [Ca2+]i than T3-supplemented cells.
    Moreover, in the T3-free cultures a significantly lower number of cells (P=0.003) responded to caffeine, a typical activator of sarcoplasmic reticulum Ca2+-release channel.
    T3-deprived cardiomyocytes also presented altered morphology with larger dimensions than T3-supplemented cells (P<0.0001).
    Additionally, in T3-deprived samples α-sarcomeric actinin and SERCA-2 protein levels were reduced to 65.6±3% (P<0.0001) and 74.1±4% (P=0.005), respectively, when compared with the T3-supplemented group.

    Conclusions:
    Our data show that human cardiomyocyte calcium handling and phenotype are strongly influenced by T3 suggesting important implications of the ‘low T3 syndrome’ on the progression of heart failure.
     
    sb4 and Ema like this.
  2. pattismith

    pattismith Senior Member

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    My trials with T3 and cortisol have lead me to the conclusion that I have intracellular calcium flux abnormalities in my muscles and brain cells.

    I only found transient but total relief of my symptoms when supplementing with T3 and prednisolone, but mostly losing the good effect when supplementing on a regular basis.

    I experimented that a hugh emotional stress associated with T3 and cortisol is doing a great job to relieve my symptoms, so i have to investigate why I benefited so much from this association.

    When the stress was lower, i was back to the broken doll state....So I found this article and decided to try again caffeine.

    I have taken it in the past, but it made me worse, and this phenomenon was more marked with time going by.

    I had to take a full cup of coffee to get the effect, while still supplementing with T3 but miracle, it worked!

    So coffee and stress may have the same effect!

    So caffeine, a typical activator of sarcoplasmic reticulum Ca2+-release channel, doesn't work well if cells are T3 deprived, but the association is working!


    This makes me think that my main problem is a dysfunction of this sarcoplasmic reticulum Ca release channel, with a T3 insufficiency/blockage.

    I still can't say why T3 alone can't do the job and my journey to recovery is far from finished, but I am now able to manage a bit more my disability, and to have more control on it, so I have hope!
     
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  3. Ema

    Ema Senior Member

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    Have you ever tried nimodipine?
     
  4. pattismith

    pattismith Senior Member

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    no I don't have access to it in my country, but I doubt it would help me.

    Nimodipine is blocking sarcoplasmic reticulum Ca channels, whereas drugs that have shown to help me are activators of these channels (T3 + caffeine).


    Thyroid hormone regulates Ca(2+)-ATPase mRNA levels of sarcoplasmic reticulum during neonatal development of fast skeletal muscle.

    Abstract
    In gastrocnemius muscle from newborn rats the mRNA for the fast sarcoplasmic reticulum (SR) Ca(2+)-ATPase isoform (SERCA1) comprised over 90% of total SR Ca(2+)-ATPase mRNA content and increased 5-fold between day 5 and 20 after birth, whereas in hypothyroid muscle the SERCA1 message level remained constant. Triiodothyronine (T3) treatment of 2-day-old euthyroid rats induced a precocious stimulation of SERCA1 mRNA levels, indicating that T3 is the determining factor in the stimulation of SERCA1 message levels and that this stimulation underlies the previously reported effect of the thyroid status on the neonatal development of SR Ca(2+)-ATPase activity. The low mRNA level for the slow SR Ca(2+)-ATPase isoform (SERCA2) was constant in both euthyroid and hypothyroid muscle development. Nevertheless, T3 treatment of hypothyroid neonates induced a transient stimulation of SERCA2 message levels, indicating that SERCA2 is responsive to higher levels of T3.


    Thyroid hormone differentially affects mRNA levels of Ca-ATPase isozymes of sarcoplasmic reticulum in fast and slow skeletal muscle.

    Abstract
    mRNA levels for the type I and type II isoforms of sarcoplasmic reticulum (SR) Ca-ATPase were determined in soleus (SOL) and extensor digitorum longus (EDL) muscle of euthyroid (normal), hypothyroid, and hyperthyroid rats. Total Ca-ATPase mRNA content of hyperthyroid muscle was 1.5-fold (EDL) and 6-fold (SOL) higher compared to hypothyroid muscle, with corresponding increases in total SR Ca-ATPase activity. EDL contained only type II Ca-ATPase mRNA. In SOL type I mRNA was the major form in hypothyroidism (98%), but the type II mRNA content was stimulated 150-fold by T3, accounting for 50% of the Ca-ATPase mRNA in hyperthyroidism.
     
  5. Ema

    Ema Senior Member

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    Am I reading this wrong then? It doesn’t sound like it antagonize those channels, but (at high doses) stimulates them.


    This effect does not exclude additional cytosolic sites of action. In addition to its sarcolemmal action, nimodipine was shown to stimulate Ca2+ sequestration in skeletal and cardiac sarcoplasmic reticulum vesicles (11). Because this effect was observed only at concentrations ( M) considerably higher than that required for its sarcolemmal effect, the cytosolic sites of action of nimodipine probably are not relevant for its therapeutic activity. Nimodipine was also found to stimulate Na+-K+-dependent ATPase (57). Therefore, the possibility exists that in addition to its effects on the entry of Ca2+into the cell, nimodipine may also facilitate CaZ+efflux.


    https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1527-3466.1985.tb00479.x
     
  6. pattismith

    pattismith Senior Member

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    Nimodipine is a Calcium channel blocker, which decreases cytoplasmic calcium level, it is a L-type VGCC blocker
     
  7. Ema

    Ema Senior Member

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    Yes, but it appears that is doesn’t only act that way. That was my question.
     

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