Professor Pete Jones is a physiology researcher at the University of
Otago. His lab focuses primarily on the control of calcium within the heart and brain. This fundamental approach allows his research to touch on multiple pathologies; heart failure, arrhythmias, seizure disorders, and dementias.
The difficulty when researching these disorders is that they are progressive or spontaneous in nature. In order to have a full picture of the function of a heart developing heart failure, or a brain developing dementia, you need to be able to monitor its function over a long period of time. Arrhythmias and seizures are sporadic, so you need to be recording continuously to ensure nothing is missed.
By integrating Kaha Biopotential Telemeters into their work, Pete’s lab have been able to record EEG and EKG without battery-life issues or time restrictions. This addition to the Jones Lab has been the latest step toward understanding
"The Kaha Telemetry System is reliable, and a great long-term investment"
how calcium signalling changes over the course of these disorders, and how long treatments might take to get them back on track. We sat down with Pete to learn more about his work, and how he’s finding the Kaha telemetry system.
Our Interview with Professor Pete Jones
My research is really interested in how calcium controls how cells work. We are trying to understand what causes calcium signaling to go wrong, both in the heart and the brain.
My work started in the heart. The movement of calcium is what drives every contraction of the heart. When calcium is released, the heart cells contract, and the heart contracts. Then, when calcium goes down, the heart relaxes.
This is really important because the amount of calcium dictates how hard it contracts. So, when you’re exercising, you get lots of calcium, causing a really strong contraction. Whereas, when you want to control your rhythm, you can release that calcium more often.
In many diseases, this goes wrong. For example, in heart failure, you don't get enough calcium released, so the heart doesn't contract very well. And if you release the calcium at the wrong time, you also get beats at the wrong time; that's a really common cause of arrhythmias.
Now, in the brain, we're not getting a contraction of the cells, but that same release of calcium is what's driving their excitability. This is also going to be involved in how well the cells can talk to one another.
Again, if we see changes in that calcium release in the brain, we get altered neuronal function. This has been associated with seizures and also with dementias.
A protein through which this calcium is released is called the ryanodine receptor. This receptor is a protein that's located on a calcium reservoir within the cell. When you’re healthy, calcium is only released when we want it. So, in the heart, about once a second, and in the brain, enough to allow these cells to communicate. If you get changes in the structure of that protein, calcium gets released at the wrong time. Hence, you get arrhythmia in the heart, and you get altered neuronal activity in the brain.
We've spent a lot of time looking at mutations in that protein. These are really well-known to cause arrhythmias in patients. They've more recently been associated with epilepsy and Alzheimer's disease in the brain.
So, because we're looking at changes in the electrical signal caused by these changes in calcium, we want to use EKG recordings to look at arrhythmias in the heart, and we want to use EEG recordings to look at seizures, and also changes in brainwave activity associated with dementia.
Everybody knows dementia is really common, Alzheimer's in particular, but also people will be fairly aware that the treatment options are really limited and the issue becomes not only when do you treat the disease, but also when can you diagnose the disease; because of course you can’t start treatment until you know it is happening.
One of the hopes is by measuring EEGs, we might get some early indicators that these animals are going to progress into a more severe form of the disease. This, in theory, could be translated to patients. By using more detailed EEG monitoring we might be able to identify those patients that are most likely to progress the fastest into disease.
If we combine this with our work looking at the treatment of Alzheimer's disease, these are the patients we could potentially put on our drug study earlier in the process to try and stop that deficit in memory and the other complications that come with the disease. This is a major concern for New Zealand. We're getting older. Thankfully, we’re not getting other diseases as often, but that means that as our population gets older and older we’re going to need more treatments for neurodegenerative diseases.
We’re using the Kaha system to do really long recordings. Most of the time with these systems you can record for a short period of time in blocks, and that can be really useful in certain types of disease research, like when you’re giving a stimulus to trigger a result. Whereas, if you’re looking at more chronic diseases such as heart failure and arrhythmias or neurodegenerative disease, you can’t take these snapshots.
A big limitation of previous research is that you can give an animal a heart attack to change its cardiac function, then record for an hour or two, and then your data is done. You do another experiment where you record for an hour or two, but you do it two days later, or a week later or a month later, but you’re missing everything in between. What we can now do is record continuously to see how the function of the heart is changing over time.
This is even more important when we start thinking about neuronal function. Alzheimer’s disease, for example, progresses over weeks and months. Currently, all of the research looking at brainwave activity, especially in rodent models, looks at these snapshots or it has to use a triggered response. What we can do with Kaha telemetry is measure these spontaneous seizures over massive lengths of time. We can see how they change over time, how they might build up, and how they change the function of the animal.
I think one of the biggest reasons we chose Kaha was the ability to do long-term recordings. We had previous experience using other systems which were battery based, and they can work well for short periods of time. The battery systems are never going to allow you to record for months, but they can record for weeks. The ability to have telemetry that is wirelessly charged is something that was unique to Kaha.
It was also a big benefit to be able to record in parallel. We’re doing both EEG and ECG recordings. This means we can have eight animals recording EEGs and eight animals recording ECGs. The telemetry itself is agnostic. It doesn’t care what it’s recording. So, it’s really useful to have one system that allows us to measure these different physiological processes instead of making us choose one measurement over another.
We were also just familiar with ADInstruments systems. The software was familiar, the support was familiar, and that was a really important thing to us, it allowed us to get stuff working quickly.
That was another main benefit of choosing Kaha; that support system. When you’re using a more advanced system, you expect technical challenges. Some of these challenges were simply setting up the system so we could do long-term recordings, or setting up the system so we could do many recordings in parallel. The other part is how much data you obtain.
If you’re recording EEG data for 20 weeks in a row you’ve got phenomenal amounts of data to process. Because that amount of data isn’t typical there aren’t really hard and fast rules on how to do this, and not a lot of software can handle it either.
What’s been really good about working with ADInstruments is that they recognize this difficulty, and we’ve been really fortunate to work with members of the support team to help us streamline analysis. We’ve been sending data backwards and forwards, developing new algorithms to help us process it all. It’s still a work in progress, but that support has saved masses of time compared to doing it manually over and over again.
Our current work takes a mechanistic approach; we’re trying to understand the basis of arrhythmias, of seizures, of dementia. What we’ll be moving onto next is the treatment of these diseases.
We’re starting to do some of these studies already. We’re starting to treat some of our animals that have seizures with drugs. They’re not just going to stop having seizures on day one, but the ability to do long-term recordings allows us to do interventions and follow them over time, so we can actually see if a treatment reduces the occurrence over time as the drugs build up in their system.
