MemberHey, 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.
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."
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.
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...
The article you mentionned is anterior to hamann/page findings as said by @rtwombly
Dude the answer to the glutamate thing is in the first quote, it's funny coz you're the second one I give it and who re-ask the same thing.
No Rage (jk I don't mind to help!)First link, page 11, just read the title it's what you want.
"KATP channels in glutamate mediated synaptic degeneration"
It's the echo of a very old article (1999 aka Tinnitus stone age):
http://www.ncbi.nlm.nih.gov/pubmed/10842598
Third link is also talking about the phenomenom in a more subtle manner. The thing is also you should not look for glutamate as a keyword but more VGLUT, but this is a very (very) complex mechanism you want to dig into. I don't want to introduce the notion of solute carrier, gene expression, transporter balance, etc... It would get insanely messy for everyone.
If you have the courage and want to be super hardcore:
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035955
It's by Hamann & friends
Then read this:
http://www.ncbi.nlm.nih.gov/pubmed/23581566
And this baby:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860955/
You'll understand exactly how it works.
PS:
You seem to be motivated to do some research, I was thinking building a wiki for tinnitus, with the entire process with each step documented, we could do several level of complexity starting by super macro view and going into super deep details, would you be interested to help, or any science lover out there ? @jazz , @locoyeti , @attheedgeofscience , @dan, @rtwombly ,@Mpt ,@Zimichael others ??
Sorry to hear you didn't get on either. I don't have any intention to play around with drugs. My question was more from an inside perspective of what the drug looks like, it's chemical make-up , compounds etc for my own personal understandings. Thanks for the info.
