I'm finding pregnenolone to be beneficial a few times a week. It activates this. Wonder if it helps it to work better? May also explain why GastroCrom has been such a help. It has a mild calcium channel blocking affect. If calcium isn't going into cells properly with this dysfunction - maybe why this helps. Wonder where the connection with MCAS comes in? Tramadol also helps me and is a mild calcium channel blocker. This dysfunction also affects glutamate function and Tramadol also works on NMDA function. More research to do......
Issie
I'm totally confused by this research, at the moment, to be honest.
I had it backwards in my head that the channels were increased, not reduced as it clearly states, and that intracellular calcium was thus high. High intracellular calcium is a hallmark feature of MCAS which is probably why calcium channel blockers like verapamil can prove useful (and Gastrocrom as well, to some extent).
But I'm completely confused...Vickery says in her blog post that mefenamic acid is an activator of the TRPM3 channel. But it's not. It's a nearly complete inhibitor. Yet she reports that the Griffiths team are reporting some amount of success using that drug to block the channel, regardless? And that is apparently the supposed recommendation by the researchers?
Pregnenolone is a strong activator. I can't seem to tolerate it much at all lately. But the articles I read seem to indicate that the activation happens at super-physiological doses, not the doses seen in the body. And that makes some sense, because pregnenolone certainly has a function as a neurosteroid and hormone precursor that would at least seem to be more important than being a calcium channel activator.
So I'm scratching my head a bit, at the moment, trying to figure out what it all means and if/how it all ties together.