TRPC and other TRP channels, channelopathies, and kidney disease.
Magnesium and sialic acid get a mention too, and ankyrin repeat domains. G protein taste receptors seem involved with TRP channel fu but more research is needed (or I still need to find it).
I added an addition to the last post: Addition - after sleep: Take home point I didn't add in my half-asleep state: Drink more coffee for the niacin and because the polyphenols in coffee promotes calcium excretion - if hyperinflammation is a problem. But my gut can’t take coffee anymore. Making the sub-point that pomegranate peel is likely protective against kidney injury for similar reasons - bitter taste receptors help regulate some types of TRP calcium channels similarly to the butyrate/niacin GP109 receptor. GP-coupled receptors have exterior and interior sections - a message on the outside can cause an action to happen within the cell.
Moving on - too much calcium entry can cause apoptosis of the kidney podocyte. Abstract:
Over a decade ago, mutations in the gene encoding TRPC6 (transient receptor potential cation channel, subfamily C, member 6) were linked to development of familial forms of nephrosis. Since this discovery, TRPC6 has been implicated in the pathophysiology of non-genetic forms of kidney disease including focal segmental glomerulosclerosis (FSGS), diabetic nephropathy, immune-mediated kidney diseases, and renal fibrosis. On the basis of these findings, TRPC6 has become an important target for the development of therapeutic agents to treat diverse kidney diseases. Although TRPC6 has been a major focus for drug discovery, more recent studies suggest that other TRPC family members play a role in the pathogenesis of glomerular disease processes and chronic kidney disease (CKD). This review highlights the data implicating TRPC6 and other TRPC family members in both genetic and non-genetic forms of kidney disease, focusing on TRPC3, TRPC5, and TRPC6 in a cell type (glomerular podocytes) that plays a key role in proteinuric kidney diseases. (Hall, Wang, Spurney, 2020)
In a hyperinflammation state, more magnesium is needed. The body will take it from the bones - but that also frees calcium - so then the body has a bigger problem - what to do with the excess risky calcium? Cover it with cholesterol spackling and try to get rid of it along blood vessel walls. The blood level of calcium has to stay within a narrow range for safety.
Cholesterol is not the bad guy for heart health as much as lack of magnesium and excess inflammatory calcium.
The food supply is lower in niacin than it used to be for a more meat-eating population. Niacin is one of the few B vitamins that is common in protein foods, not just grains or beans like other Bs. The food supply is also lower in bitter tasting phytonutrients as the food industry removes them to increase consumer palatability. the food and supplement supply also tend towards high calcium and low magnesium. The “Upper Limit” for tolerance was set fairly low for magnesium as it can cause an obvious symptom of diarrhea/watery stools if too much is taken at once. The decision was old and mentioned a need for further study to clarify the guidance - that didn’t happen it seemed from what I read. Our nutrient guidelines are often based on older material that included estimates and best guesses meant to be further studied - but wasn’t.
Truly, veterinarians know more about nutrition than Medical Doctors (MDs) on average, it seems to me. If you took your pet to a vet and the pet kept getting worse, would you keep going back? Probably not, yet people regularly accept the worsening health found with medical care.
People with kidney disease that wastes magnesium may be prescribed a 400 mg magnesium supplement three times a day - space it out for bowel tolerance. From my outsider perspective - nephrologists seem to know the most about electrolytes and physiology, of the various specialist fields of medical care.
TRPC (canonical) channels respond to mechanical pressure or are activated by a combination of phospholipase C and a G protein coupled receptor. (Hall, Wang, Spurney, 2020)
“All TRPC ion channels are calcium permeable, but the channels are poorly selective, with permeability ratios (PCa/PNa) that vary significantly between family members [26]. The calcium influx is stimulated following receptor-induced phospholipase C (PLC) activation in response to both tyrosine kinase receptors (TKRs) and G protein coupled receptors (GPCRs) [27].” (Nilius, et al, 2007 [27], as cited by Hall, Wang, Spurney, 2020)
Dysfunction in TRP channels has been found to be involved in a number of conditions which are now sometimes referred to as channelopathy conditions. (Nilius, et al, 2007) Nociceptive pain is considered a channelopathy by some researchers.
Types of TRP channels in mammals include: “TRPC (canonical), TRPM (melastatin), TRPV (vanilloid), TRPA (ankyrin), TRPP (polycystin), and TRPML (mucolipin) are the only identified subfamilies in mammals.” (Fig. 1, Nilius, et al, 2007) They all are permeable to calcium with varying levels of selectivity except for TRPM4 and TRPM5. Some also seem to be able to release excess calcium if there is too much in the cell from the organelle’s release of it. Intracellular and extracellular messengers can modify the channels flow along with changes in temperature, or chemical or mechanical pressure. Light can also be an activator for channels linked to rhodopsin. (Nilius, et al, 2007)
“TRPC channels also contain three or four NH2-terminal ankyrin repeats (349).” (Nilius, et al, 2007)
FYI - chimeric spike S1 subunit negatively effects ankyrin repeat domains on TRP channels. This is likely a risk factor in the hearing changes seen with CoV issues and may be a factor in the kidney risks too. Preventing the fusion cleavage is a big therapeutic goal for treating chimeric spike issues. The S1 and the S2 subunits can do far more harm once separated from each other. Pomegranate peel is possibly a fusion inhibitor (seen with HIV) which would prevent the ripple effects of damage from the separate subunits.
TRP ankyrin repeat domains provide a spring like effect for the channels that likely is involved in detecting pressure changes. The prion like aspect of S1 subunit may be causing misfolding of the complex protein coil (many ankyrin units are repeated and together form the spring like complex - roughly).
I have been trying to pass on the message that topical magnesium or chelated magnesium supplements are likely needed. GI absorption of ionic magnesium requires TRPM 6 and 7 channels however this source says they don’t have ankyrin repeat domains. (Nilius, et al, 2007) Maybe just additional magnesium is needed due to the hyperinflammation. Magnesium helps keep some types of TRP channels closed to calcium entry.
TRP channels are environmental detectors and can play a role in sour taste detection and may activate some types of G proteins.
“Such a mode of activation might mimic the physiological stimulus that activates the complex. TRPP3 and PKD2L3 form a receptor for sour taste (176, 184).” (Nilius, et al, 2007)
The jabs cause 10,000 times more spike production than a typical infection (based on memory, not sure of the reference). The fact that Trump supports the jabs suggests he is a patsy or in on it. Yet, he is being made the Messiah to save us by the Q (seeming) channels on Telegram and elsewhere.
What is going on? Big con? In the mean-time, chimeric spike is bad, um kay, (-SouthPark guidance counselor), and anyone who doesn’t get that is questionable as a source of information - either they are gullible or complicit. Neither of those would be reliable as a helpful guide.
Channelopathies may be due to - 1) gene differences, 2) physiological changes in TRP channel abundance and sensitivity, or 3) increased metabolites produced in inflammation affects TRP channel function.
(1) “Channelopathies are traditionally defined as diseases coupled with identified defects in the gene encoding the channels. Following this definition, five TRP channel-related channelopathies have been identified to date.
(2) However, perturbation of physiological functions mediated by ion channels can also contribute more subtle to the genesis of several diseases. Such effects may be provoked by changes in channel abundance, or channel sensitization, or desensitization, resulting in exaggerated, or diminished, responses to various pathological stimuli.
(3) Abnormal endogenous production of various agents during the development of a disease (for example, in inflammation or autoimmune conditions) can affect channel function in a manner that contributes to the progression of the disease. Many members of the TRP superfamily are potential targets for such pathogenic factors. Abnormal regulation of ion channel function is especially interesting in all forms of inflammation and in systemic diseases, such as neurodegenerative, cardiovascular, and respiratory diseases. TRP channels are exceptional in the sense that they are often polymodal, i.e., they are activated by multiple and diverse gating stimuli and act as molecular integrators of these external and/or internal signals.” (Nilius, et al, 2007)
[*Numbers, bold, and the division of the paragraph into three parts are edits that I added for emphasis.]
Polyphenols and other bitter tasting phytonutrients are likely essential for health because they play a role in TRP channel regulation. Bitter taste receptors are G protein coupled receptors. The over-arching tone/attitude within medical research regarding bitter taste receptors is to view them as something on the tongue that helps protect us from ingesting toxins. They are more than that is my impression - bitter taste sensitivity (10,000 times more sensitive than other taste receptors) is our self-medicating guide to lead us to tastes that make us feel better because of the functional effects throughout the body that bitter taste receptors perform for us. A wounded animal seeks out the plants that make them feel better. Humans can do that too when not inhibited from listening to their instincts.
When I was sick with CoV in early outbreak - the respiratory symptoms approached asthma, and I had had that before, so knew I would need an inhaler if it got worse. The talk at that time (March 2020) was still vents, vents, vents, and I didn’t need to be one the people that needed one of the limited supply. I found a research article about Nigella sativa and citrus peel against SARS-1, so I tried citrus peel and it worked amazingly well. (Adequate zinc is needed in order to have bitter taste receptors.) While sick, the pith of an entire Navel orange plus the fruit was my serving. As I got better, half the orange seemed adequate. The urge to eat it just faded as I was eating. The timespan was short enough that I noticed the change. How had one whole orange seemed perfect, and now it seemed like too much? My needs had changed, is the likely answer and my tongue/body is smart enough/self aware enough to recognize that.
In early childhood, over squelching children’s curiosity is inhibiting them for the rest of their lives from being self-learners, curious and problem solving in their approach to life.
Bruce Lipton has likened the cell membrane to our ultimate “brain” - our membranes are our sensory specialist and allows or prevents interaction with the environment based on the sensations perceived - when functioning.
Bruce Lipton - The Cell Membrane (Youtube).
He mentions that the polysaccharides on the surface of cell membranes are negatively charged which would help repel positively charged particles like the chimeric spike protein or activated Lipid Nanoparticles. In order to have those positively charged branching “sugar trees” (his descriptor), we need to be able to make sialic acid and/or polysialic acid. We need nucleotides and N-acetyl-glucosamine in order to do so. See: Sialic acid and TRP channels. (substack.com)
Another video of his started playing and it is helpful for tackling those early childhood messages that impact the rest of our lives.
Dr. Bruce Lipton Explains How To Reprogram Your Subconscious Mind, (Youtube).
How to rewrite your subconscious mind - (1) Hypnosis - tapes listened to during sleep/falling asleep. (2) Create a new supportive habit and practice it repetitively - say the positive things even if they aren't really your belief yet - say "I am happy" so often that it becomes embedded. (3) See other resources on his site brucelipton.com.
The attitude of gratitude is being happy about the things that are nice, instead of dwelling on the negatives that need change. I am warm, fed, have no worries about not being warm and fed tomorrow - life is pretty good. I plan to take an Epsom salt soak today - life is very good.
My early childhood trauma left me with messages of being bad and deserving punishment and no affection - erroneous messaging that it turns out is common among people with early childhood trauma (toddler or younger - the viewpoint at that age is that everything that happens is caused by the child). We have to get a little older to recognize that others are separate beings from us and we are not causal of everything that happens. All these poor children growing up in CoV era likely feel at fault for the Scamdemic and may have a hard time giving up face masks after having been forced to wear them for so long.
Disclaimer: This information is provided for educational purposes within the guidelines of Fair Use. It is not intended to provide individual guidance. Please seek a health care provider for individualized health care guidance.
Reference List
(Hall, Wang, Spurney, 2020) Hall, G.; Wang, L.; Spurney, R.F. TRPC Channels in Proteinuric Kidney Diseases. Cells 2020, 9, 44. https://doi.org/10.3390/cells9010044 https://www.mdpi.com/2073-4409/9/1/44/htm
(Nilius, et al, 2007) Nilius, B.; Owsianik, G.; Voets, T.; Peters, J.A. Transient receptor potential cation channels in disease. Physiol. Rev. 2007, 87, 165–217. https://journals.physiology.org/doi/full/10.1152/physrev.00021.2006
Bruce Lipton - The Cell Membrane (Youtube)
Dr. Bruce Lipton Explains How To Reprogram Your Subconscious Mind (Youtube)