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on skin and the senses
How might sensory signaling function in skin cells?
CATERINA: Nerve terminals are very closely squeezed in between skin cells, and lots of sensory neurons express receptors for chemicals like ATP, glutamate, histamine—many of the things that might be produced in the skin. The skin is also the largest organ in the body, it’s exposed to the environment, and it rapidly replaces itself, so it would make a nice antennae. The hypothesis is that when heat-gated channels in keratinocytes get activated, they release something that is diffusing right next door to waiting sensory neurons, and that this is one way the nervous system is being activated. It’s a nice idea—we’re trying to figure out whether there’s any truth to it. We have some data to suggest that we’re on the right track. For instance, if we increase the expression level of these heat-gated channels in skin cells, under the correct circumstances we can observe enhanced heat-evoked pain behavior.
Do you have any candidates for what these skin cells might be releasing that is signaling to sensory neurons?
CATERINA: We think that at least one of the signals transmitted from keratinocytes to sensory neurons is prostaglandin E2, a molecule involved in pain sensation, inflammation, and the maintenance of skin integrity. The synthesis of prostaglandins is the target of drugs like ibuprofen and aspirin, and we have found that these drugs can block the enhanced pain behavior we usually see in our animals that express more of these heat-gated channels in their skin cells. We don’t think that prostaglandin E2 is the only signal, but we think it is one signal.
What are some of the other projects going on in your lab?
CATERINA: One question has to do with how these sensory ion channels respond over time to continuous stimulation. Most people view ion channels as being very specific for certain ions that they let into or out of the cell. What we have discovered, which wasn’t anticipated, is that if these channels are stimulated for a relatively prolonged period of time, one to two minutes, the composition of ions going through the channels changes. This phenomenon implies that not only can quantitative characteristics, like the number of channels or the likelihood that they will signal, be changed, but also qualitative characteristics, like the particular ions going through the channel and the particular biological response that you might get. We’re trying to understand how that works and what that might mean in the context of the cell.
Has the current funding situation affected the kinds of questions or which questions you are pursuing in your lab?
CATERINA: It’s slowed us down, because there are experiments that we think would represent a very good way of approaching these questions that we just can’t afford to do the way that they should be done. If we had more flexibility financially, we might be able to answer these questions a little faster. The other way it’s slowed me down is that it’s made me be very cautious about hiring. Although we’d love to be doing fifteen things at once, you need to have a funding stream that is going to secure people for a number of years. For either a postdoctoral fellow or a graduate student, you need to be able to make a long term commitment when you hire somebody in the lab.
Michael Caterina | How We Sense Heat and Pain
Michael Caterina's research