The Inner Ear Battery and Cx26

So much for weekly updates! In my last blog entry (51 weeks ago) I wrote about how the Connexin 26 protein was used to make Gap Junctions, which in turn allow things to pass between cells. But I wasn't really sure of the role they had in hearing. I thought it might be to do with allowing electrical signals to pass between cells. Turns out I may have been wrong 😲.

I've done a bit more reading in the year since. turns out these so-called experts don't really know. There's a few theories out there though. Some researchers now think that the main role of Cx26 in hearing is to do with the Potassium cycle, and the Inner Ear Battery.

Part of the ear acts like a big battery. The energy from this battery is used to turn small hair vibrations into big electrical pulses that the brain converts to our perception of sound. The charge in the 'ear battery' is carried by Potassium ions. The theory is that without Cx26, the Potassium ions build up in the hair cells, and they die.

Potassium ions are usually referred to as K+. (K is the atomic symbol for Potassium, and the + means it has a positive charge because it is missing an electron). There is a membrane in the ear, one one side you have lots of K+, the other side has less. The K+ wants to get to the side with less. This happens when you hear something, and it causes the Voltage across that membrane to change. This change in voltage drives a signal along the nerve cells to the brain.

The process of how K+ gets across the membrane, and back again, is called the Potassium Cycle. K+ ions pass through the hair cells in the ear and back again. How exactly this happens is uncertain, but some think Gap junctions play a major role, specifically those built using Cx26, and possibly Cx30 as well.

I am not sure exactly why K+ build up causes the hair cells to die, maybe the charge form the ions interferes with other chemical reactions necessary for cell life. I have read that Cx mutations cause inner ear cells to die soon after the onset of hearing (while the fetus is still in the womb), so it doesn't take them long to die.

I'll finish on something cool - scientists have already tapped the 'ear battery' to get an electrical current, which was used to power electronics. Maybe one day they can use this to power hearing aids and cochlear implants. Read about it in the LA times

There you have it - more confused ramblings! If you want more authoritative info on the ear battery, check out this page from Baylor College of medicine. And if you want to know why I'm so confused check out this paper on Gap junctions and the Potassium Cycle

Gap Junctions

The first thing to figure out is what healthy Cx26 actually does. Connexin 26 is a type of long molecule called a protein. It has another name: Gap Junction Beta 2. The mutation that causes my son's deafness is on a part of the DNA that makes this protein, which is why it is called the GJB2 gene.

So what is a gap junction?

Cells are basically bags of stuff - DNA, RNA, mitochondria, all sorts of sciency sounding stuff inside that make life as we know it happen. They are kind of like tea bags - water can pass through the outside of the cell (the cell membrane), and also oxygen and CO2, but not much else.

Stuff needs to get in and out of cells for life to happen. They need chemicals to do what they need to do - otherwise why would we eat? They also need to communicate to each other, and this is typically done through electrical signals; by passing ions (electrically charged atoms or molecules) between each other.

This is where gap junctions come in. Gap junctions are like tunnels connecting cells, allowing materials to pass between them.

Here's a picture robbed straight from Wikipedia:

 The blue plates are the edge of two cells, and the gap junctions are the yellow structures linking them together. From the top down, they look like a flower, with 6 petals. And each one of those petals is a Connexin protein.

A bit more about how the gap junctions work. There are many types of Connexin proteins, 21 in humans, and the gap junction can be made up of all the same type or different ones.

Half of a gap junction is called a connexon - note the second 'o'. When two cells are in contact, a connexon forms at the edge of each cell, and they connect to form a junction. The two connexons linking up don't have to be the same.

So from different combinations of Connexin proteins and connexons you can get different junctions, and these will let different materials through. From what I've read, the gap junctions made with Connexin 26 transport Potassium ions as well as some (unspecified) small molecules. This would suggest to me that these gap junctions are mostly used to send electrical signals between cells.

This fits in with my basic understanding of hearing: hair cells being wiggled by sound waves and sending a signal via nerve cells to the brain. If Connexin 26 is critical in sending these electrical signals, than I can imagine how not having it might cause deafness. But GJB2 mutations can cause other problems, particularly relating to skin growth, so maybe I'm off the mark.

One thing I would like to find out; how come GJB2 mutations don't necessarily cause profound deafness? They must be fairly critical for hearing, so why is there any hearing at all if they are not around? I suppose I can't answer that until I know their role.

The Question Remains

My son was discovered to be deaf at the young age of 5 weeks. A few months back, genetic testing showed that this was due to a genetic mutation - specifically the gene GJB2, which creates the Connexin 26 protein.

At the time, I had never heard of GJB2, or Connexin. The test results contained a lot of terminology and codes which I still haven't decrypted. The Dr. dealing with us, while friendly and supportive, didn't seem too knowledgeable either. Any question we asked lead to her immediately consulting google.

So this is what I did for the next few days. There was a lot of information out there, but it fell into two categories. The first was mostly articles from scientific journals, unreadable in a similar manner to the genetics results letter I received. The second category was the kind of overly simplistic stuff seen in hospital leaflets. It scratched the surface in terms of an explanation, but left me with more questions than answers. I wanted Goldilocks information.

My big question, and one I couldn't easily find a clear answer to is the following: What role does Connexin play in the hearing process, and how does the GJB2 mutation cause hearing loss?

I could find partial answers to this, but each one lead to more and more questions. So I started digging further, and am now stuck in a rabbit hole of genetics, cell molecular biology, and structural anatomy, none of which I really understand. But I m slowly trying to get to grips with it.

My aim is to update this blog weekly until I fully understand every aspect of the relationship between GJB2, Connexin 26 and deafness. Which will presumably be for a very long time.

My homework for next week:  GJB2 = Gap junction beta 2. So what the feck is a gap junction?

[p.s. if you are in the middle of doing your own research into this I found this link to be a good starting point]