[ using juvenile Drosophila melanogaster (fruit fly)] Knocking-out (deactivating) the parkin gene in Drosophila influenced energy metabolism, neuronal resting potential, synaptic development, and kinesis. More specifically, ATP (the universal cellular energy currency) synthesis and oxygen consumption were significantly reduced, and elevated levels of reactive oxygen species were observed. These physiological and metabolic changes suggest that mutations in parkin results in a neuronal energy deficit which underpins bradykinesia.

Current concepts on the development and pathogenesis of Parkinson’s disease focus heavily on the involvement of oxidative stress in inducing cell death in the substantia nigra. Although experimental evidence exists to demonstrate the vulnerability of dopamine neurons to damage by reactive oxygen species, it has remained unclear as to whether the oxidative stress is a consequence of the disease or initially causes the disease. To definitively elucidate the role of oxidative stress in causing the neurophysiological defects observed by mutating the parkin gene, the parkin mutants were initially treated with ‘reactive oxygen species scavengers’, antioxidants which either donate an electron or remove an electron from the reactive species to neutralise their effects on the cell. Surprisingly, introducing scavengers did not restore the resting membrane potential of the neurons or affect the locomotor defects of the mutant juvenile Drosophila, thus suggesting that these defects derive from causes other than oxidative damage.

The wild-type parkin gene was then exploited as a ‘transgene’, and was over-expressed in a parkin mutant to confirm the energetic cause for bradykinesia. Introduction of the wild-type gene entirely restored wild-type functionality. The finding conclusively demonstrates that oxidative stress occurs downstream in the pathology of Parkinson’s disease and cannot therefore be the underlying cause, but simply a product of the neurodegenerative process...

... This demonstration, and the conclusion that metabolic impairment of neurons rather than oxidative stress induces the neuronal damage leading to locomotor disorders, marks a considerable benchmark in our understanding of Parkinson’s disease ...
http://www.theyorker.co.uk/lifestyle...chnology/12300

I am researching calcium metabolism dysregulation in association with PD onset. Specifically increased permeability of the cellular membrane, leading to both loss of hydration and loss of intracellular calcium into the extracellular space.
anyone else considered calcium dysregulation in relation to PD?
I think there is direct involvement of the parathyroid gland.

thanks, madelyn

So one wonders then what causes the metabolic impairment? Does this piece of the puzzle get laid next to the piece involving circadian rhythm disruption and endocrine involvement? I tune into this board almost like the parkinson mystery is a who done it and we are all in this together tring to find out: who killed mr. Body in what room with what weapon? There are so many brilliant posts, so much compassion expressed and so much assistance for those of us newly diagnosed. Thanks to this poster and everyone on the board for all this positive energy and tireless scientific curiosity.

olsen-
Along with calcium, I have some questions about the other electrolytes, particularly potassium. The latter moves between cell and serum in response to insulin in much the way that glucose does. I have not looked at calcium. Have you?

Olsen,

We took a trial run at taking dynacirc, a calcium channel blocker which has been studied in regards to PD, I think by Northwestern. I hate to say, we could not tell any difference, and quit taking it. Interestingly, one of our neuros, when we told him we wanted to try it, said if he had PD it might be one of the things he would try, too. We were very optimistic when we heard this but as I said, could not see any benefit once we began taking it. Maybe we did not take it long enough? But one can only take so many pills every day

From wikipedia:
Glucose in the body increases after food consumption. This is primarily due to carbohydrate intake, but to much lesser degree protein intake ([1])([2]). Depending on the tissue type, the glucose enters the cell through facilitated or passive diffusion. In muscle and adipose tissue, glucose enters through GLUT 4 receptors via facilitated diffusion ([3]). In brain, kidney and retina, glucose enters passively. In the beta-cells of the pancreas, glucose enters through the GLUT 2 receptors (process described below).
Two aspects of this process are explained below: insulin secretion and insulin action on the cell.


Insulin Secretion process
Insulin secretion
The glucose that goes in the bloodstream after food consumption also enters the beta cells in the Islets of Langerhans in the pancreas. The glucose passively diffuses in the beta cell through a GLUT-2 vesicle. Inside the beta cell, the following process occurs:
Glucose gets converted to Glucose-6-Phosphate (G6P) through Glucokinase; and G6P is subsequently oxidized to form ATP. This process inhibits the ATP sensitive potassium ion channels of the cell causing the Potassium ion channel to close and not function anymore. The closure of the Potassium channels causes Depolarization of the cell membrane causing the cell membrane to stretch which causes the voltage-gated Calcium channel on the membrane to open causing an influx of Ca2+ ions. This influx then stimulates fusion of the insulin vesicles (bubble like structure with insulin in them) to the cell membrane and secretion of insulin in the extracellular fluid outside the beta cell; thus making it enter the bloodstream...

In addition:

Trigger mechanism

Insulin is secreted in the beta cells of the islets of Langerhans. Before secretion, insulin is synthesized. Once insulin is synthesized, the beta cells are ready to release it in two different phases. As for the first phase, insulin release is triggered rapidly when the blood glucose level is increased.
The second phase is a slow release of newly formed vesicles that are triggered regardless of the sugar level. Glucose enters the beta cells and goes through glycolysis to form ATP that eventually cause depolarization of the beta cell membrane (as explained in Insulin secretion section of this article). The depolarization process causes voltage controlled calcium channels (Ca2+) opening and allowing the calcium to flow into the cells. An increased calcium level causes activation of phospholipase C, which cleaves the membrane phospholipid phosphtidyl inositol 4 into inositol 1 and diacylglycerol. Inositol 1,4,5-triphosphate (IP3) binds to receptor proteins in the membrane of endplasmic reticulum (ER). This allows the release of (Ca2+) from the ER via IP3 gated channels, and raises the cell concentration of calcium even more. The influx of Ca2+ ions push the Insulin molecules (that are inside their "bubble" surrounding) outside of the cell.
Therefore, the process of insulin secretion is an example of a trigger mechanism in a signal transduction pathway because insulin is secreted after glucose enters the beta cell and that triggers several other processes in a chain reaction.
http://en.wikipedia.org/wiki/Insulin..._blood_glucose
Unsure if this answers your question.
I recall a discussion concerning hypokalemic periodic paralysis; interestingly A calcium channel mutation causes hypokalemic periodic paralysis.

I have felt a difference taking a liquid calcium , magnesium , zinc &d3 from Earth Fare.
Seems we can use supplements more easily in liquid form ...... besides the fact they are easier to swallow!!