thanks, ron, the anti-hypertensives being discussed DECREASE the BBB permeability--makes sense now....madelyn

I am curious about what the calcium ions in these neurons are doing when they replace sodium ions. I think of sodium ions as primarily being responsible for propogating the "action potential" which occurs when a neuron is activated. Both calcium and sodium ion concentrations are much higher outside cells than inside.

What fascinates me is the fact that the major sources of calcium ions in tissues is the extracellular fluid and the mitochondria. The cell membrane at rest is relatively impermeable to both calcium and sodium ions, where any "leakage" of these ions is reversed by active channels, or pumps. During an action potential, the membrane becomes transiently more permeable to sodium ions. I'm not sure about what happens to calcium ions then.

I plan to get the Nature paper and read it to find out more.
Robert

by turning down the activity of voltage-dependent calcium channels responsible for an autonomous "pacemaking" function. That same function is performed in JUVENILE mouse neurons by another type of pacemaking channel which relies on sodium ions. This unique pacemaking activity is key to the steady release of dopamine by these neurons that is required for maintaining motor control. This "takeover" by these calcium channels in older mice is aggravated by the increased calcium inside the cells which can be caused by toxins (rotenone, MPTP, etc) that disrupt mitochondrial function and/or structural integrity. Other sources of increased intracellular calcium are also possible in highly metabolically active cells such as these under stress.

Presumably, in the absence of such challenges, the adult cells can go right on using their pacemaking calcium channels and remain healthy.

The drug (israpidine) binds to the calcium channels, forcing the neurons to revert to the juvenile sodium-dependent pacemaking channels which are still present but not dominant in the adult. The resulting drop in intracellular calcium apparently makes the neurons less susceptible to stress challenges, especially those which result in the production of superoxide ions and other reactive oxygen species which can cause cell damage and death.

What is not known is whether the same scenario prevails in primate/human dopaminergic substantia nigra neurons as in mice. If so, the drug could be useful for neuroprotection in people known to be susceptible to developing PD. It is unlikely that the drug can contribute to neuroregeneration, the replacement of neurons that have already died.

I was highly impressed with the science and experimental elegance of this work.

Robert

You have to register, but anyone can still view Dr. Surmeier’s remarks from the Forum:

http://www.parkinsonsaction.org/content/view/77/84/

Mary M. Richards
Director of Government Relations
Parkinson's Action Network
phone 202.638.4101 ext103

I live in Jordan. Isradipine i not available. I wonder if I can use another type of calcium blocker such as Adalat which is available in Jordan. I will greatly appreciate input on this question. Thanks to all contributors on this thread.

So what has happened in the meantime?

Robert Bert

Robert,

i still take dynacirc cr -- nearly 3 years and counting. does it work? no idea. but it's been quite a while since i've had to adjust my meds - maybe 2 years? my progression is slow.

i plan to write to dr surmeier and tell him - plus let him know that I have had 4 spect scans and maybe they would be helpful to him even though i'm not in a controlled study.

jean

Please forgive me if I'm totally off base here, I don't quite understand everything said on this post but I have a question. The post from Olsen said;

All neurons in the brain use electrical signals
to do their job, much like digital computers.
First, Surmeier observed that dopamine neurons are non-stop workers
called pacemakers. They generate regular electrical signals seven days
a week, 24 hours a day, just like pacemaker cells in the heart.


I was told that metal filling cause "short circuiting" in the brain. Does this have anything to do with making problems for these neurons?

Again, sorry if I'm making you scratch your head and thinking "What?"

Tina

"Test drug seen as best hope in decades for tackling Parkinson's"

This was the headline from the press release I posted here two years ago but I can find nothing about any human trials for Iradipine anywhere.

Does anyone know anything??

Chris

http://clinicaltrials.gov/ct2/show/NCT00753636

Link to information about recruiting for Phase II study at Chicago last July.