USAP-DC

This project studies how the proteins of the nerves and muscles of fish that live in Antarctica function in the cold, which should provide information on the function of these same proteins in all animals, including humans. These proteins, called ion channels, open and close to allow ions (atoms or molecules with electrical charge) to flow into or out of cells which causes the electrical activity of nerves and muscles. Mutations that influence this process are the basis of numerous human disorders such as epilepsy, heart arrhythmias, and muscle paralysis. Thus, it is important to understand what parts of the proteins govern these transitions. The speed with which channels open and close depends on temperature. Human ion channels transition slowly when we are cold, which is why we become numb in the cold. Yet Antarctic fish, called icefish, are active at freezing temperatures that drastically limit the activity of human ion channels. The investigators have evidence that specific alterations in the icefishs' ion channels allow their channels to operate differently in the cold and they will use gene discovery and biophysical methods to test how these changes alter the transitions of icefish proteins at different temperatures. The project will also further the NSF goals of training new generations of scientists and of making scientific discoveries available to the general public. The gene discovery analysis will be done by undergraduate students including those from a minority-serving university and the investigators will develop a new course which will also serve students at that institution and elsewhere. In addition, the investigators will participate in educational outreach events with the general public as well as with groups with special needs. Notothenioid fishes are one of the most successful groups of vertebrates in Antarctica. Notothens have adaptations to the freezing water they inhabit and this project will study how their voltage-gated ion channels (VGICs) function in the cold. The molecular movements of ion channels are severely impaired by cold, yet notothens function at temperatures that would paralyze the nerves and muscles of "cold-blooded" temperate zone animals. Surprisingly, no biophysical or molecular investigations have been conducted on notothen VGICs. The investigators have preliminary data that amino acid substitutions occur at sites in VGICs that are evolutionarily conserved from fruit flies to humans. Some of these sites are known to impact channel function and the role of others in channel transitioning are unknown. The results from studying them will provide novel information also applicable to non-notothen, perhaps even human, VGICs as well as providing insights into how VGICs adapt to the cold. The project will biophysically characterize notothen VGICs using voltage-clamp techniques will and compare their properties over a range of temperatures to the same channel from two temperate zone fish. The role of unique notothen amino acid substitutions will be characterized by mutagenesis. One specific aim will be a project in which undergraduates mine notothen sequence databases to identify other potential amino acid substitutions in VGICs that might facilitate adaptation to the cold.

Person	Role
Zakon, Harold	Investigator and contact
York, Julia	Researcher

Antarctic Organisms and Ecosystems

Award # 1443637

USAP-1443637_1

None in the Database

Repository	Title (link)	Format(s)	Status
Texas Data Repository	Evolutionary analysis of transient receptor potential (TRP) channels in notothenioid fishes	Not Provided	exists
GenBank	TagSeq tissue specific expression data for Antarctic Harpagifer antarcticus and tropical African cichlid Astatotilapia (Haplochromis) burtoni	Not Provided	exists
USAP-DC	Functional characterization of temperature activated ion channels from Antarctic fishes	None	exists

1. York, J. M. (2023). Temperature activated transient receptor potential ion channels from Antarctic fishes. Open Biology, 13(10). (doi:10.1098/rsob.230215)
2. Julia M York, Harold H Zakon, Evolution of Transient Receptor Potential (TRP) Ion Channels in Antarctic Fishes (Cryonotothenioidea) and Identification of Putative Thermosensors, Genome Biology and Evolution, Volume 14, Issue 2, February 2022, evac009 (doi:10.1093/gbe/evac009)