Retigabine (Trobalt, Potiga) — General Discussion

[SteveToHeal]

Hi @cdog ,

Thanks for your comment, it's pretty late here in montreal, so I'll be short
(EDIT: I wanted to be short, but I could not resist writing a lot lol, I am such a failure haha)

I think I already covered this question a few weeks ago, maybe this is what you're looking for:
If not we can obviously discuss more in a dedicated thread or in the private chat.




I'll make an additional comment on the action potential:
Basically when you touch your hand you feel it, the nerve is transmiting an electrical message through the spine to your brain.

This is basically the action potential, so when you hear a sound, the information is transmited to your brain in a similar fashion.

Imagine each cell (axone) is closed by a membrane (voltage gated channels):

Outside you have sodium, inside you have potassium, it's a resting state.
View attachment 2640

When you have a stimuli, sodium goes in through the sodium gate and it changes the sign, it's the depolarization
View attachment 2641
Then potassium gate open to let potassium out and change the sign again it's the repolarization
View attachment 2642

Then the sodium potassium pump evacuate the remaining sodium and the cell becomes ready for another cycle
View attachment 2640

The entire cycle looks like this:
View attachment 2643


Now what happens when you have T., the potassium voltage gates don't work very well, and don't let the potassium go out correctly, it means the sign never totally change and a continuous signal is transmited to the brain, in other word Tinnitus.

If you look at the document from dr hamann:
http://www2.le.ac.uk/departments/cpp/staff/dr-martine-hamann/hamann-neuroscience-group

This is what they are talking about, the signal become heratic, burst and shit and cannot go in rest mode.

All of this because of a defficient potassium channel: Kv3.1.

The glutamate create what we call otoxicity and this phenomenon affect the potassium channels, it's locked by platicity in a very short time (days, maybe weeks).
They proved that on chicken
http://www.nrronline.org/article.as...olume=7;issue=9;spage=714;epage=718;aulast=Yu

If a drug comes and forces the specific potassium channels to act normally, plasticity will lock in the other way and those axone will be able to go in rest mode, in other words, let you experience silence again.

Hope this help !
Now I go to bed, it's 3am and I give class tomorrow morning haha ^_^

That is awesome. Thank you for taking the time to explain this in layman's terms. Do you think Autifony's drug AUT00063 will do this exactly? If so, i'm booking my ticket now!

 

[undecided]

Excellent post @benryu, makes me wanna shower myself with trobalt, lol

 

[Mpt]

Hi @cdog ,

Thanks for your comment, it's pretty late here in montreal, so I'll be short
(EDIT: I wanted to be short, but I could not resist writing a lot lol, I am such a failure haha)

I think I already covered this question a few weeks ago, maybe this is what you're looking for:
If not we can obviously discuss more in a dedicated thread or in the private chat.




I'll make an additional comment on the action potential:
Basically when you touch your hand you feel it, the nerve is transmiting an electrical message through the spine to your brain.

This is basically the action potential, so when you hear a sound, the information is transmited to your brain in a similar fashion.

Imagine each cell (axone) is closed by a membrane (voltage gated channels):

Outside you have sodium, inside you have potassium, it's a resting state.
View attachment 2640

When you have a stimuli, sodium goes in through the sodium gate and it changes the sign, it's the depolarization
View attachment 2641
Then potassium gate open to let potassium out and change the sign again it's the repolarization
View attachment 2642

Then the sodium potassium pump evacuate the remaining sodium and the cell becomes ready for another cycle
View attachment 2640

The entire cycle looks like this:
View attachment 2643


Now what happens when you have T., the potassium voltage gates don't work very well, and don't let the potassium go out correctly, it means the sign never totally change and a continuous signal is transmited to the brain, in other word Tinnitus.

If you look at the document from dr hamann:
http://www2.le.ac.uk/departments/cpp/staff/dr-martine-hamann/hamann-neuroscience-group

This is what they are talking about, the signal become heratic, burst and shit and cannot go in rest mode.

All of this because of a defficient potassium channel: Kv3.1.

The glutamate create what we call otoxicity and this phenomenon affect the potassium channels, it's locked by platicity in a very short time (days, maybe weeks).
They proved that on chicken
http://www.nrronline.org/article.as...olume=7;issue=9;spage=714;epage=718;aulast=Yu

If a drug comes and forces the specific potassium channels to act normally, plasticity will lock in the other way and those axone will be able to go in rest mode, in other words, let you experience silence again.

Hope this help !
Now I go to bed, it's 3am and I give class tomorrow morning haha ^_^

you mean Jastebroff's music of the brain theory is flawed?... how is that possible?... what a joke, the tinnitus community has been done such a disservice by therapy charlatans peddling treatments based on nothing but theories with no scientific backing, the ATA will probably be posting research on sodium/pottasium channels in 10 years or so---

 

[Mpt]

Hi @cdog ,

Thanks for your comment, it's pretty late here in montreal, so I'll be short
(EDIT: I wanted to be short, but I could not resist writing a lot lol, I am such a failure haha)

I think I already covered this question a few weeks ago, maybe this is what you're looking for:
If not we can obviously discuss more in a dedicated thread or in the private chat.




I'll make an additional comment on the action potential:
Basically when you touch your hand you feel it, the nerve is transmiting an electrical message through the spine to your brain.

This is basically the action potential, so when you hear a sound, the information is transmited to your brain in a similar fashion.

Imagine each cell (axone) is closed by a membrane (voltage gated channels):

Outside you have sodium, inside you have potassium, it's a resting state.
View attachment 2640

When you have a stimuli, sodium goes in through the sodium gate and it changes the sign, it's the depolarization
View attachment 2641
Then potassium gate open to let potassium out and change the sign again it's the repolarization
View attachment 2642

Then the sodium potassium pump evacuate the remaining sodium and the cell becomes ready for another cycle
View attachment 2640

The entire cycle looks like this:
View attachment 2643


Now what happens when you have T., the potassium voltage gates don't work very well, and don't let the potassium go out correctly, it means the sign never totally change and a continuous signal is transmited to the brain, in other word Tinnitus.

If you look at the document from dr hamann:
http://www2.le.ac.uk/departments/cpp/staff/dr-martine-hamann/hamann-neuroscience-group

This is what they are talking about, the signal become heratic, burst and shit and cannot go in rest mode.

All of this because of a defficient potassium channel: Kv3.1.

The glutamate create what we call otoxicity and this phenomenon affect the potassium channels, it's locked by platicity in a very short time (days, maybe weeks).
They proved that on chicken
http://www.nrronline.org/article.as...olume=7;issue=9;spage=714;epage=718;aulast=Yu

If a drug comes and forces the specific potassium channels to act normally, plasticity will lock in the other way and those axone will be able to go in rest mode, in other words, let you experience silence again.

Hope this help !
Now I go to bed, it's 3am and I give class tomorrow morning haha ^_^

one question I have is how does this phenomenon explain permanent tinnitus spikes in volume because it appears to me based on the anecdotal evidence on this site that individuals already suffering with tinnitus have a much higher chance of getting further increases in volume than those people without tinnitus have of getting tinnitus

 

[iAzra]

Seriously, i think people using earplugs for 'everyday use' hurt their ears more than save them.. No proof, just my thoughts.

Yes, but when you live in a capital you never know when there'll be noise like ambulance sirens, car alarms, house alarms, screeming children, subways, railways, road work etc. It is all damaging to the hearing.

 

[dan]

That is awesome. Thank you for taking the time to explain this in layman's terms. Do you think Autifony's drug AUT00063 will do this exactly? If so, i'm booking my ticket now!

Yes, that's what he thinks....Would that be British Airways or Westjet sir ?

 

[Viking]

you mean Jastebroff's music of the brain theory is flawed?... how is that possible?... what a joke, the tinnitus community has been done such a disservice by therapy charlatans peddling treatments based on nothing but theories with no scientific backing, the ATA will probably be posting research on sodium/pottasium channels in 10 years or so---

Jasterboff is a charlatan .... as others unfortunately .... In agreement with the major distribution companies of wearable sound generators or environmental. Starkey, Oticon, Re sound and many others. They spend pennies to build hearing aids that cost us € 2000 .... clinical results in at least 18/36 months ........... HAHAHAHAHHAA! In Italy I do not know .... NO ONE NO ONE who has benefited from this type of "therapy". I am in contact with many people who have spent at least 800 euro to hire the sound generators and have them returned after a maximum of three months because they were worse.

 

[SteveToHeal]

Jasterboff is a charlatan .... as others unfortunately .... In agreement with the major distribution companies of wearable sound generators or environmental. Starkey, Oticon, Re sound and many others. They spend pennies to build hearing aids that cost us € 2000 .... clinical results in at least 18/36 months ........... HAHAHAHAHHAA! In Italy I do not know .... NO ONE NO ONE who has benefited from this type of "therapy". I am in contact with many people who have spent at least 800 euro to hire the sound generators and have them returned after a maximum of three months because they were worse.

mine are lying dormant.

 

[SteveToHeal]

Yes, that's what he thinks....Would that be British Airways or Westjet sir ?

i ain't no sir

 

[benryu]

Hey! Thanks for the feedbacks I really appreciate.

@undecided haha don't shower yourself with trobalt. I have simplified things an awful lot here. There is not only one type of potassium gate, there is actually a lot, and T. seems to affect only one specific type the Kv3.1. Trobalt acts on some Kv7 channels. Each channel has a specific function in the action potential process.
http://en.wikipedia.org/wiki/Voltage-gated_potassium_channel

I kind of described that in a old post.

• Despite a drug being potassium channel opener, it has to be very precise to work.
• Flupirtine doesn't act on any sub unit related to T. ( So no possible impact)
• Retigabine acts on interspike interval, meaning less T. spikes and it can possibly repolarize the action potential for some people. But the sub unit range is too wide with numerous side effects. (so it can work to stabilize T. and decrease it to some extent, but is not specific enough to be viable.)
• AUT00063 acts directly on the repolarization and is much more precise, so it's a viable solution providing it works as expected

Also the sign is not absolute negative or postive, let's say its a relative negative or positive. (eg: +20% negative in comparaison with the equlibrium)


@SteveToHeal , yes this is what the AUT00063 is supposed to do.
http://www.autifony.com/publications/Turner-et-al-2013-vWeb.pdf


@Mpt , I believe there is a lot of ways to approach the problem, and I am not saying my version is the truth. It's just my interpretation of the issue based on the scientific evidences I found and my own experience.

Now I don't believe much in all those "shamanic" treatment that are not supported by a lot of scientific work.

Today only 3 approaches have demonstrated potential through scientific evidences:
-Chemicals therapy (AM-101, AUT-00063)
-Cell therapy (either with stem cell injection or gene activation to force auto repair)
-Chirurgy (in some specific T. cases)

For the likeliness of increase in T. among T. sufferers it's quite simple:

First the hair cells are like a forest after a storm, some trees are broken, some other are about to break, meaning smaller winds can cause damage to the nearly broken trees.

Second as said previously this is not absolute signs, and the gate keep working but not as well as before. And plasticity may consolidate in the wrong way over the time to put it simple.

EDIT: this is why I expect inertia with the AUT00063, and why they will probably want recent T. in their study (a few months old max), the more solid the plasticity "consolidation" is in one way, the longer it takes to revert it and stabilize it the other way and finally reconsolidate as expected.

 

[Lisa88]

@benryu
Re your note just above to MPT.
Can I clarify with you that some etiologies of t are not due to hair cell damage and/or hearing loss ... i.e. not an inner ear disorder?
And secondly, the opening of potassium channels could potentially work for any t case?
I know you refer to this earlier a little in the thread, but any clarification you could give would be helpful.
Thanks, @benryu
Lisa

 

[Zimichael]

Sheeeeesh!!! I have just spent an hour or more going back over this thread to where I left off and headed for the mountians - which slammed me right into the 50 meter long article on GABA and Glutamate, etc. posted by @dan on August 6th...Ha, ha!
Two cups of good organic coffee later I am slowly handling things in a semi linear fashion (with occasional sighs of pristine streams, peaks, and altitudinal memories...so forgive me if I'm not on the ball here) and am going to just do some bullet points observations/questions, seeing as I was pretty involved in this Retigabine hunt before absconding.

1. I could go back and hand out about 50 "hugs, agrees, winners, hearts, hugs" to all of you giving so much time, attention, help, advice, etc. to this thread...and others of course. AWESOME! (Lame word but seems to fit!)

2. In same vein I publicly announce my "love" for @benryu as per Rhea and others. The Hey my divorce is final in 2 weeks, but I'm not moving to Canada! Kidding = "bro" kind, and just incredible appreciation for your dedication to helping us with complex neurological esoterica and your knowledge. I am learning so much from you. Also agree about the similar kudos for @attheedgeofscience.

3. Man, compared to my tinnitus (and H) Christian's and Viking's seem much more "complicated" or something. As some of you know [see my Profile] I have had T. for 58 years but it was the ototoxicity of 2006 and the fourth level of increase in 2012 that have been the biggest challenges. Within all that my T has stayed completely constant in volume once the 'new higher volume' occurred at each jump up. So...I suspect there may be differences to what seems to happen to Christian and Viking where their T seems to go all over the place even without Trobalt/Retigabine. Ummmm...apologies if I got this wrong guys.

4. @Lep regarding blurred vision. I took a shit load of meds of all types during 7 years of undiagnosed chronic illness and blurred vision was a pretty common initial effect I recall. HOWEVER I am in no way saying it may be 'insignificant' for you re the Retigabine. Just an observation.

5. @Telis and @benryu ...Availability of Trobalt! You may recall that I actually had/have a prescription from my doc and tried to get it filled here in N. California and could indeed do so, but the pharmacy only wanted to order a full mega box as they knew no-one else would want the stuff. So the initial $270 or whatever (as not covered by my Obamacare insurance) for a month's supply was going to end up being nearly $1,000 or whatever for gobs of the stuff...which I did not want to do. Not being super rich and all.
However, my ever helpful doc's assistant then said she would order it for me c/o Canada at this site, with prices even cheaper than my initial 'cheap' quotes from CVS pharmacy here in California:

http://www.canadapharmacyonline.com/DrugInfo.aspx?name=Potiga6804

Ezogabine - also known as Trobalt (Retigabine)

ProductManufacturerDosageQtyPrice(USD)

Potiga Known as Trobalt outside the USGSK50 mg84$148.00

Potiga Known as Trobalt outside the USGSK100 mg84$149.00

Potiga Known as Trobalt outside the USGSK200 mg84$269.00

Potiga Known as Trobalt outside the USGSK300 mg84$359.00

So...seeing as I split for the hills, is this a bullshit pharmacy??? Do they not have it in Canada??? Yet my doc's office has used this particular pharmacy for a bunch of US patients who had no insurance and wanted lower prices for meds, thus I am wondering what is going on with this??? Did anyone try them???

And to sum up...Potiga IS AVAILABLE here in the USA and the cash price is no that bad IF you want a huge supply (rather than trail amount). Also it's available free from GSK if you do not have drug insurance coverage and have low income. [See my earlier posts on "patient assist" re all the major drug companies]. However, you must have a prescription.

6. Yeah, benzos (glutamate action) for sure do not reduce T volume long term, they just calm you down short term. The only drug I am on is 1 mg of Klonopin/Clonazepam for sleep, but after years it does absolutely bugger all for that, but I can't drop it currently as it kicks anxiety in if I lower it and I need to have a good long steady spell before I taper any more. Just a human around seems to nullify the 'visceral anxiety response' but that is not my reality any more re living alone and pretty isolated....Also there was some speculation in this thread that taking a benzo plus Retigabine may help the Potassium channels thing, so maybe not a big deal to be off it for a trial.
I need to re-read all that aspect though re K channels, Sodium channels and Glutamate, etc. as it is a bit dense for my brain at present and I may have the Benzo aspect wrong re this. However, it is now clear that the "bad Glutamate excitation" thing for acute, short term audile destruction stuff is more than clear (thanks @benryu!!!) and finally I have a handle on all that aspect my doc was working on some years ago, but way too late. I have now shown him how his 'neuroexcitation' glutamate tendencies for treatment are pretty much irrelevant after the amount of time since I got hit by the meds and such in 2006. Seems like K channels are where it's at for us longer term T'ites!

7. Last question...SO WHO IS ON THE DRUG NOW??? Is it just Christian and Matt? And maybe Lep???
As I can get back on board and try this stuff as have the green light on the prescription and the Canada prices are OK for my budget. However, I'm wondering why so few others are on it unless it is only due to 'terrified docs' refusing to write scrips?! My doc (who has a chronic illnesses practice with about a dozen other MD's, ND's, OD's, etc.) saw the light right away and realized the risks were 'longer term' and well within the boundaries of "OK" for a short term therapeutic trial. We do have a long term relationship and he knows I'm not an idiot so will taper real slow, but it sounds like lots of others on this thread have such relationships with docs or medical professionals - so am I missing something??????

OK, long enough post and excuse the pedantic format, but was the best way I could see to update myself and you all...as yes, I am still a candidate for 'guinea pig' status here and picking up where I left off, but was hoping there would be a dozen more of you on it by the time I got back from my "mountain high".

Ahhhh...stretch, yawn, creak and crack. That 50 pound pack was a bear to load up those steep rock passes, but not bad for my little 64 year old frame! Ha, ha...Not quite ready to "Potiga it" today...need a bit more "re-integration" time I think.

Best to all, and again many, many thanks to all you dedicated T helpers.

Zimichael

 

[Viking]

Thank you for your respect and support

 

[benryu]

@Zimichael , thanks a lot for the message, I ready to start our bromance anytime, just let me know a few weeks in advance so I can divorce too.

I'll have a look at the retigabine, but I am puting this on hold while I go on holidays in september. Almost 1 month in hawaii ! yay !

Back to the topic to answer @Lisa88 question

@@benryu
Re your note just above to MPT.
Can I clarify with you that some etiologies of t are not due to hair cell damage and/or hearing loss ... i.e. not an inner ear disorder?
And secondly, the opening of potassium channels could potentially work for any t case?
I know you refer to this earlier a little in the thread, but any clarification you could give would be helpful.
Thanks, @@benryu
Lisa

To make it simple a Tinnitus goes under one of this two umbrellas:

Neurogical (everything related to ototoxicity either with drug or glutamate excess after loud sound, anything that affects potassium channels such as head trauma, aging etc..)
Mechanical (tumor pressure, blood circulation issue, dental issue, TMJ, etc...) That can be treated if the origin of the problem is solved.

The first category is always the expression of potassium channel dysfunction, this the only way for your auditory cortext to generate T.

The second issue can depend on multiple factor but T. is just a symptom that disapear. (Eg: brain tumor removed make T. disapear.

Potassium channel will work for the first category only, no matter the time frame.
Glutamate blocker will work only in case of recent trauma, may provide a protection for chronic sufferers.

 

[dan]

@Zimichael
Potiga cannot be SOLD in Canada - it is banned for sale in Canada and you cannot get a prescription for it in Canada. That's why myself, @benryu, @Telis, @all Canadians, cannot get a hold of it here.
In order for us to get it, we would need to leave Canada, find a US/foreign doctor who will prescribe it for us, and then we would need a mailing address outside Canada for Canadapharmacyonline to send the stuff. I hope that clarifies things better.

P.S.
An @benryu 4month Potiga course would cost at least $1500USD at those prices.
That is still too much for me.
I want to know if Mexico sells Trobalt/Potiga. Can anybody help me find out. Ty.

 

[benryu]

@Zimichael
Potiga cannot be SOLD in Canada - it is banned for sale in Canada and you cannot get a prescription for it in Canada. That's why myself, @benryu, @Telis, @all Canadians, cannot get a hold of it here.
In order for us to get it, we would need to leave Canada, find a US/foreign doctor who will prescribe it for us, and then we would need a mailing address outside Canada for Canadapharmacyonline to send the stuff. I hope that clarifies things better.

P.S.
An @benryu 4month Potiga course would cost at least $1500USD at those prices.
That is still too much for me.
I want to know if Mexico sells Trobalt/Potiga. Can anybody help me find out. Ty.

I found Potiga in Dominican republic but I don't trust them and I don't want to risk to take some crap. I would avoid Mexico if I were you.

 

[Lisa88]

@Zimichael , thanks a lot for the message, I ready to start our bromance anytime, just let me know a few weeks in advance so I can divorce too.

I'll have a look at the retigabine, but I am puting this on hold while I go on holidays in september. Almost 1 month in hawaii ! yay !

Back to the topic to answer @Lisa88 question



To make it simple a Tinnitus goes under one of this two umbrellas:

Neurogical (everything related to ototoxicity either with drug or glutamate excess after loud sound, anything that affects potassium channels such as head trauma, aging etc..)
Mechanical (tumor pressure, blood circulation issue, dental issue, TMJ, etc...) That can be treated if the origin of the problem is solved.

The first category is always the expression of potassium channel dysfunction, this the only way for your auditory cortext to generate T.

The second issue can depend on multiple factor but T. is just a symptom that disapear. (Eg: brain tumor removed make T. disapear.

Potassium channel will work for the first category only, no matter the time frame.
Glutamate blocker will work only in case of recent trauma, may provide a protection for chronic sufferers.

Thanks so much. I am assuming neither of these categories need to be associated with inner ear/hearing loss. So potassium channel openers can work for those with and without hearing loss.

 

[dan]

@Zimichael and others:
Question-
What does "no insurance" mean as per GSK criteria. I have "free" national healthcare in Canada, but they do not cover ANY medication under their plan, only seeing a doctor is free and surgeries.
Would I qualify for free Potiga under GSK program?

 

[benryu]

Thanks so much. I am assuming neither of these categories need to be associated with inner ear/hearing loss. So potassium channel openers can work for those with and without hearing loss.

Correct you can have T. without hearing loss, and hearing loss without T.

 

[Lep]

@Zimicheal actually I'm not on Retigabine but I want to restart therapy.I'm going to talk with my neurologist in a few days.

 

[dan]

no reason why Dominican Republic or Mexico are bad. As long as the drugs are vaccum sealed and labelled on the blister pack and the box, there is no way to fake them.

@benryu - can you find out the same way you did for Mexico? I would REALLY appreciate it bro.

 

[benryu]

no reason why Dominican Republic or Mexico are bad. As long as the drugs are vaccum sealed and labelled on the blister pack and the box, there is no way to fake them.

@benryu - can you find out the same way you did for Mexico? I would REALLY appreciate it bro.

My mother is a Professor in Dominican Republic, so she looked up for me, she told me there is a lot of fake drug coming from india there. I doubt I could find it in Mexico with my network.

 

[rtwombly]

@Mechanical (tumor pressure, blood circulation issue, dental issue, TMJ, etc...) That can be treated if the origin of the problem is solved.

@
Hmm. I wonder if persons with a mechanical cause for their tinnitus will be able to benefit from something like retigabine, with its spike-inhibiting behavior, but not AUT00063, since repolarization would only last until the next re-injury through that mechanical cause.

I think my tinnitus may have originally been caused by teeth clenching at night, but I believe I've stopped that behavior since. The damage that was done is what I'm hoping these drugs will correct.

 

[Mpt]

one question that I have out of curiosity-- autifony has published the chemical patent for their drug with the chemical formula-- how hard would it be to get a lab somewhere to "manufacture" the compound- as it wouldn't be manufactured for sale, it wouldn't be breaking a US patent,- I guess this could apply to all drugs currently in trial states

 

[benryu]

one question that I have out of curiosity-- autifony has published the chemical patent for their drug with the chemical formula-- how hard would it be to get a lab somewhere to "manufacture" the compound- as it wouldn't be manufactured for sale, it wouldn't be breaking a US patent,- I guess this could apply to all drugs currently in trial states

Do you have a link, I am curious to see what it looks like.

 

[dan]

@benryu , how much is the drug cost in the D.R. ?

 

[attheedgeofscience]

http://www.sigmaaldrich.com/life-science/cell-biology/cell-biology-products.html?TablePage=9551103

 

[benryu]

@benryu , how much is the drug cost in the D.R. ?

Very similar to the pricing above in the canadian pharmacy.

 

[cdog]

I'll make an additional comment on the action potential:
...
If not we can obviously discuss more in a dedicated thread or in the private chat.

Hey, thanks for the graphical explanation

After reading some more wiki, I think I more or less understand now - IF the potassium channel is blocked, repolarization takes longer than usual (it still occurs via the sodium/potassium pumps), and therefore the membrane remains depolarized for longer, which means Ca2+ channels are activated for longer, and finally the Ca2+ sensitive neurotransmitter containing vesicles are more prone to releasing the neurotransmitter. In other words, neuron is more likely to fire and for a longer time.

Now what happens when you have T., the potassium voltage gates don't work very well, and don't let the potassium go out correctly, it means the sign never totally change and a continuous signal is transmited to the brain, in other word Tinnitus.

If you look at the document from dr hamann:
http://www2.le.ac.uk/departments/cpp/staff/dr-martine-hamann/hamann-neuroscience-group

This is what they are talking about, the signal become heratic, burst and shit and cannot go in rest mode.

Yes, read the paper quoted on that page http://www.sciencedirect.com/science/article/pii/S0378595511002620 and that pretty much states explicitly what I was asking about. For example,

"Our findings now show that the intrinsic electrical properties of FCs in the DCN are modified following exposure to loud sound. After AOE, a proportion of FCs exhibit a distinct bursting firing pattern, and thereby lose the ability to fire regularly or at high firing frequencies. Our results suggest that one mechanism contributing to this change of activity is the down regulation of HVA K+ currents in FCs." (Section 4, Discussion).

This more or less fits well with the explanation of how Kv channels slow down the repolarization, and therefore take longer to fire again (i.e. decreasing the firing frequency). The paper confirms this - "High voltage activated K+ currents enable cells to fire at high rates" and "By activating at depolarized potentials and rapidly deactivating, HVA K+ currents facilitate action potential repolarisation and lead to a short action potential duration. We found that FCs with a bursting pattern of firing exhibited significantly longer action potential decay times compared to unexposed FCs, which is consistent with a down regulation of HVA K+ currents."

The glutamate create what we call otoxicity and this phenomenon affect the potassium channels, it's locked by platicity in a very short time (days, maybe weeks).
They proved that on chicken
http://www.nrronline.org/article.as...olume=7;issue=9;spage=714;epage=718;aulast=Yu

Are you sure that is the right paper? I scanned through it, but couldn't find any mention of potassium channels.

As for how acoustic over exposure (AOE) induces fusiform cell (FC) bursts (related to blocked Kv channels, I presume) - the paper has a speculative section about that too (section 4.4). They say it could be due to "homeostatic adjustment" in the DCN (dorsal cochlear nucleus), but to fully understand that explanation I think I would have to do more research.

If a drug comes and forces the specific potassium channels to act normally, plasticity will lock in the other way and those axone will be able to go in rest mode, in other words, let you experience silence again.

I hope so. The paper authors are very cautious in their conclusion (section 4.5) : "It is likely that tinnitus starts at the peripheral level and evolves throughout the central auditory pathway via a process that resembles memory consolidation. If this is the case, treating the first symptoms linked to acoustic over-exposure could be proven effective in slowing developing tinnitus at a later stage. The data provided here suggest that the Kv3 K+ channels in the central auditory system could be a target responsible for tinnitus at the early stages following acoustic over-exposure."

Hopefully it could also be a target at the late stages as well...

 

[rtwombly]

I hope so. The paper authors are very cautious in their conclusion (section 4.5) : "It is likely that tinnitus starts at the peripheral level and evolves throughout the central auditory pathway via a process that resembles memory consolidation. If this is the case, treating the first symptoms linked to acoustic over-exposure could be proven effective in slowing developing tinnitus at a later stage. The data provided here suggest that the Kv3 K+ channels in the central auditory system could be a target responsible for tinnitus at the early stages following acoustic over-exposure."

Hopefully it could also be a target at the late stages as well...

Bear in mind that the paper you're quoting preceded the development of a drug that could target the appropriate channels. At the time there had been no successful animal studies showing it was possible to eliminate tinnitus symptoms. We've really come a long way in a short time.