Calcium sparklets, TRPV channels and vanilla

     Calcium sparklets are not a good thing, not in excess at least. This is just a few interesting articles that have TRPV channels in common. The calcium channels cause problems in a variety of ways for some people. Identifying who is at risk for problems with fluid balance could help prevent the chronic degenerative changes that can result from electrolyte imbalance. (This post led to parts of this webpage: effectivecare.info/G3. Relaxation & Stress)
     I was amused when the search term ‘sparklets’ turned up something pertinent to my field of interest. TRPV channels and vanilloid receptors with overactive calcium flow can increase pain and other types of muscle and nerve signals.

Calcium sparklets are not a type of chewing gum. They are a sudden increase in flow of calcium through certain calcium channels in vascular tissue. A specific chemical trigger called protein kinase Calpha (PKCalpha) was found to signal L type calcium channels into increased calcium flow [3]. The sparklets occurred in diabetic vascular tissue following high blood sugar levels [2]. A cooperative action taking place with as few as three calcium channels needing to be open for maximal vasodilation to occur [1].
TRPV4 are a type of vanilloid receptor. Loss of function due to genetic difference has been associated with hyponatremia, low sodium blood levels. [6]

“TRPV4 is activated by hypotonicity in vitro, and perturbations of even a few mOsmol/kg H2O were sufficient to achieve this effect (5–7); such exquisite sensitivity closely parallels the in vivo mechanism whereby a change of only a few mOsmol/kg H2O influences release of arginine vasopressin. In rodents, TRPV4 is expressed in the blood–brain barrier-deficient central osmosensing nuclei (5, 35), and targeted deletion of the TRPV4 gene gives rise to aberrant osmoregulation in murine models (20, 21).” [6]

     Time to bake something with vanilla. The above paragraph’s reference to a blood-brain barrier deficiency having a genetic component suggests that susceptibility to headaches also could have a genetic component. The change in osmoregulation means that membranes could be more resistant to fluid and particles crossing or more open and barrierless (and  prone to get migraines). The problem could combine a deficiency in ability to transport needed nutrients into the cell with an increase in leakiness of important things out of or into the cell. The lack of nutrients like magnesium would further reduce the calcium channel blocking potential of the cell.
     So is vanilla something that some people genetically need more of? good question. And the bigger bell ringing loud was the risk of hyponatremia means that a low salt diet could lead to even lower levels of sodium in the blood.
     TRPV receptors have to do with pain control as well as flow of fluid and electrolytes (osmoregulation). Vanillin receptors can have a calming effect on the body and sooth pain. Baked goods with vanilla have a little extra besides love soothing the body. (So does hot pepper though – capsaicin).
 

Magnesium flow through the proton gates that the TRPV group of receptors control is what helps reduce  pain (when there is enough magnesium) and what causes pain signals when there isn’t enough to protect the cell interior from calcium entry. Calcium signals overwork, which leads to pain.
Calcium channel blocker medications are trying to close the gates and keep the calcium out – magnesium would be super delighted to do that if enough were being absorbed from the intestines (too full of calcium and active hormone D3).

     A study on the use of magnesium with opioid pain killers demonstrated the power of magnesium’s effect on for helping reduce diabetic pain. Diabetics normally do not find pain relief from opioids but when magnesium was given in advance the pain killer worked – and the pain killing effect continued for three days after the opioid medication effect would have worn off. The research discussion seemed to focus on using 30 mg with IVs of  morphine or other opioid and didn’t not address the fact that the 300 mg dose had reduced pain on its own, without opioid medication. [18]
 
  • by Sonkusare SK et al, Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function. Science. 2012 May 4;336(6081):597-601. [ncbi.nlm.nih.gov/pubmed/22556255]
  • Calcium and diabetic vascular dysfunction, Focus on “Elevated Ca2+sparklet activity during acute hyperglycemia and diabetes in cerebral arterial smooth muscle cells,  by Katherine M. Dunn, KM and Mark T. Nelson (11/11/09 Am J Physiol Cell PhysiolFebruary 1, 2010 vol. 298 no. 2 C203-C205) “This report is also the first to describe a molecular mechanism by which hyperglycemia produces increased [Ca2+]in VSM and suggests that this mechanism of Ca2+ sparklet activation may be uniquely initiated by hyperglycemia.”    [ajpcell.physiology.free article]
  • Article by Amberg GC et al “Calcium sparklets regulate local and global calcium in murine arterial smooth muscle” J Physiol. 2007 Feb 15;579(Pt 1):187-201. Epub 2006 Dec 7. [Free article]
  • The first three are from a search for ‘sparkles’ in pubmed, no sparkles-but autosuggester came up with ‘calcium sparklet’ and the whole list looks interesting: [ncbi.nlm.nih.gov/pubmed?term=calcium%20sparklet]-Truth can be stranger than fiction.

4. A different search ‘magnesium deficiency hyperglycemia‘ provided a summary worth reading :  Magnesium and Potassium in Lone Atrial Fibrillation, by Patrick Chambers, MD, pdf file: [afibbers.org/resources/PCmagnesium.pdf] *** this needs to be added to the IoM 1997 report on magnesium. Lefthandedness section near the bottom notes an increase calcium flow across cell membranes in left handers. A genetic difference that can lead to an increase in the isoprenoid pathway and inhibition of Na/K pumps in the membranes is suggested to occur in some left handed people. The difference can lead to an increased need for magnesium.

5. Reminder – vascular calcification is somewhat reversible and a simple way to start is to add less by limiting the amount of calcium taken in daily. Two servings a day of calcium rich foods is adequate for most people; there is also calcium in smaller amounts in many other foods too. Calcification of Soft Tissue, hardening organs and softening bones (post, 8/19/11 )

6. A loss-of-function nonsynonymous polymorphism in the osmoregulatory TRPV4 gene is associated with human hyponatremia, by Wei Tian, et al [pnas.org/content/early/2009/08/03/0904084106.full.pdf]

7. Physiology and Pharmacology of the Vanilloid Receptor, by Angel Messeguer, Rose Planells-Cases, and Anton Ferrer-Montiel (Curr. Neuropharmacol., 2006 January: 4(1) : 1-15) [link]

Excerpt:  In addition to the contribution of the vanilloid receptor as a target of the neurogenic inflammation underlying different diseases, TRPV1 is gaining interest for the treatment of neuropathic, postoperative and chronic pain and, recently, for the therapy of epithelial disorders. Thus, for instance, topical capsaicin or resiniferotoxin have been used in postherpetic neuralgia, diabetic neuropathy, postmastectomy pain and arthritis [64,103]. Recently, TRPV1 has been clearly validated as a key target for management of chronic pain in bone cancer [42]. As a result, the development of specific TRPV1 antagonists is a central focus of current drug discovery

***antagonist equals block – the vanilloid receptors are also involved in soothing – feed and educate the receptors because they all serve multiple purposes. Pain has a purpose – to signal that something is wrong. Masking pain with antagonists that deaden a function – to signal a problem – was a very disappointing climax to that paragraph. TRPV1 receptors and all the rest of the gang are very exciting – let’s not waste more money and time inventing synthetic antagonists to a message system that is very intertwined in controlling gates and flow of substance. the pain is there for a reason – starvation – lack of building blocks – lack of function.

8. More on vanilla from “Confessions of a Cardamom Addict” blogspot – blog part one–  –blog part two – ***These cover the history, processing, environmental concerns, major botanical varieties.

18(vit D bib.). [ncbi.nlm.nih.gov/pubmed/20081245] Magdalena Bujalska, Helena Makulska-Nowak, Stanis³aw W. Gumuka Magnesium ions and opioid agonistsin vincristine-induced neuropathy , Department of Pharmacodynamics, Medical University of Warsaw, Krakowskie Przedmieoecie 26/28, PL 00-927 Warszawa, Poland

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes. Thanks.

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