Professor Holly Shiels, Manchester University
Animals can form a key part of the work of investigating heart function. Holly Shiels is based at Manchester University where she studies fish. Fish are useful to study because some species can survive in both hot and cold water, or even low oxygen levels, without their hearts giving out. If we can understand how, it will help doctors to develop better therapies for humans living with heart disease. Georgia Mills dropped by Holly's lab to find out how she studies them...
Holly - We work at a number of levels. We work with whole animals, we have a swim tunnel which is a treadmill for fish. We can put the fish in the tunnel and make them exercise by changing the flow of the water that these fish must swim against and changing the temperature and oxygen concentration to try and mimic the conditions in the environment and see how that affects the ability to swim.
Georgia - Is that here by the way - could we take a look at that?
Holly - Yes...
Georgia - It is like a bathtub with a sort of tunnel that, so I guess, you can look at the fish really easily when itís swimming along there. And itís not full of water at the moment but when it is you can just pump it through as fast as you want and, I guess, really put the fish through their paces.
Holly - But the funny thing is fish love to swim so you put them in a tunnel and they just swim. We donít make them go too fast and we donít make the conditions too difficult for them, just things would experience in the wild.
Georgia - And what can this tell you?
Holly - Well the first thing we can do is to look at how they swim. The link between that and the cardiovascular system is that the heart really underlies all performance aspects of the fish, and so we can ask it to swim under different conditions. We can also put probes on the fish to measure heart function while itís swimming. The simplest is measuring EGCs or electrocardiograms that are fairly noninvasive just from the centre of the surface of the fish and we can measure ECGs or heart rates during exercise. But we can also do more invasive things: putting flow probes on, measuring pressure, measuring blood flowÖ
Georgia - What are you hoping this will tell us when you get all these readings?
Holly - Well, it will help really tell us whether or not the cardiovascular system is responsible for itís ability to swim and what aspect is it. Is it the pumping ability, is it pressure development, is it the electrical ability? That kind of leads me onto some interesting work we were doing up in the Arctic last summer. We were looking at a fish called the Arctic Sculpin. We know that thereís two populations of Arctic Sculpin. The one that was in this polar area seems to be progressively outcompeted by itís more temperate cousin, the Short Horn Sculpin. So we were looking at the sensitivity of both of their hearts to increases in temperature and we were using ECGs to look at the stability of the electrical activity of the heart as temperatures increase. So that can tell us if one species has a more electrically stable heart than the other species and, if it does, that might affect itís ability to migrate into different temperature zones.
Georgia - Before I ask you what you found out, Iíve just got to ask, applying an ECG onto a fish in the ArcticÖ this sounds like a story.
Holly - It was exceptionally interesting. We were working at a research station in the Arctic so we did have a lab and we did have the ability to try and do this. This wasnít out on a ship in the middle of the ocean. Our biggest problem was that our Sculpins started eating each other in the tankÖ
Georgia - Oh no!
Holly - So we ended up having less species by the time we got to finishing all the experiments. But it was certainly an adventure and I donít think we got the answer but, at this point, there are indications that the one with more thermal tolerance, itís heart was able to withstand higher temperatures better.
Georgia - Do we know why itís heart is better able to tolerate these changes in temperature?
Holly - Well it kind of comes to another way we do our work. So we can look at the whole heart function but we also work on the level of the single myocyte a lot of the time. Myocytes are the individual muscle cells that make up the working portion of the heart. So theyíre the parts that contract with each heartbeat and relax to allow the heart to fill. What we can do is take a heart and digest it using enzymes into these individual cells and then we can use a technique called voltage clamp or using iron imaging to look at iron flow across the cell membranes. That can tell us which of the different components that allow the heart to function are affected by the environment.
Georgia - What has this told you about what makes the heart adaptable and what doesnít?
Holly - Well I think that weíve certainlyÖ This isnít my work, this is the work of one of my colleagues in Finland, Maddy Van Eman. Heís been able to show that the sodium channel is fairly temperature sensitive and might set the ability for the heart to work at high temperatures.
Georgia - And what are these sodium channels for?
Holly - The are the channels that open in the cell that initiates muscle contraction.
Georgia - I see. So the thing that helps the heart to bumbum, bumbum at the cell level might be what is key to different species being able to do well in certain conditions?
Holly - Yes, exactly. But whatís also interesting is itís the same ion channels that control the bumbum, bumbum across all species. So whether or not weíre looking at a fish, weíre looking at a reptile, or weíre looking at mammals and humans, we still have the similar components of ion channels, and so we can use fish or reptiles really to get deeper understanding about how the heart works as a whole and, hopefully, be able to use the information there to probe or to ask questions that are relevant at the level of humans as well.
Georgia - OK. So what kind of things that might be relevant to humans have you come across so far because I know I was wondering how similar to humans is a fish heart? So what kinds of things have your found?
Holly - Well, they're certainly different at the whole heart level, but at the ion channel level thereís some similarities and, in a sense, thatís been quite instructive for the some recent work that weíve been doing looking at the effects of pollutants on the cardiovascular system. We came into this work a few years ago when we were asked to help understand the implications of the Gulf oil spill on the pelagic fish (the tuna, the mackerel), and we looked at the effects of different components of the oil.
Georgia - And what did you find?
Holly - We found that oil is not good for heart cells. It causes the cells to lose their electric ability.
Georgia - I imagine if the cells lose the ability to contract and relax at the regular intervals that they need to do that could lead to the heart not beating the way itís supposed to?
Holly - Exactly. And we also found that it also affected the calcium channels and these calciums, the ion that is actually responsible for heart contracting and for the heart relaxing, so it was affecting both the contractility and the electrical activity.