Terrance M. Egan, Ph.D.
Pharmacological and Physiological Science
Ph.D., M.I.T., 1984
University of Maryland
The lipid composition of cell membranes is a formidable barrier to the free diffusion of ions. To circumvent this barrier, cells contain membrane proteins, called ION CHANNELS, that form water-filled pores that traverse the lipid bilayer. It is the flow of ions through these channels that produces the whole cell currents that we measure in single cells using microelectrodes and the whole organ current that constitutes such clinical measurements as the EKG. Current flow through the conductive portion of the protein is controlled by changes in the conformational state of the channel. The transition of the protein from the conformation (the "open" state) that permits ions to move from one side of the membrane to the other, to the conformation (the "closed" state) that occludes the flow of ions is called "gating". My laboratory investigates the ways in which neurotransmitters and hormones control gating of ion channels in native and recombinant cardiac ion channels.
We are particularly interested in the ligand-gated ion channels that are activated by extracellular ATP. These ionotropic proteins are called P2X RECEPTORS, and we use a combination of molecular biology and electrophysiology to determine receptor domains of these proteins that are involved in ion channel gating and permeability. Our recent work suggests that the second transmembrane domain (TM2) is part of the ion pore and may contain both the gate that opens as a result of occupation of a receptor binding site by ATP and the selectivity filter that gives the channel its high calcium permeability. We have made a number of mutants in this protein domain and we are investigating the effects of these changes. We have also probed the other transmembrane domain (TM1). Like TM2, mutations in TM1 effect current flow through the pore. Finally, we are studying native P2X receptors in acutely isolated cardiac myocytes of rats and humans to determine the role these receptors play in control of cardiac excitability.
SELECTED PUBLICATIONS | Complete Listing
Samways, D.S.K. & Egan, T.M. (2011) Calcium-dependent decrease in the single channel conductance of polymodal
TRPV1 receptors. Pflüger’s Archives: European Journal of Physiology. epub ahead of
print: DOI 10.1007/s00424-011-1013-7.
Samways, D.S.K., Khakh, B.S., Dutertre, S. & Egan, T.M. (2011) Preferential use of unobstructed lateral portals as the access route to the pore of human ATP-gated ion channels (P2X receptors). Proceedings of the National Academies of Science (USA); published ahead of print August 1, 2011, doi:10.1073/pnas.1017550108.
Toulme, E, Garcia, A., Samways, D.S.K., Egan, T.M., Carson, M.J. & Khakh, B.S. (2010) P2X4 receptor specificity, functional properties, trafficking, and pharmacology of up regulated P2X responses in activated cerebellar microglia. Journal of General Physiology. 135: 333-353. PMCID: PMC2847917.
Samways, D.S.K., Khakh, B.S. & Egan, T.M. (2009) ACCELERATED PUBLICATION: Tunable calcium current through TRPV1 receptor channels. Journal of Biological Chemistry. 283:31274-31278. PMCID: PMC2581567
Samways, D.S.K, Migita K., Li, Z. & Egan, T.M. (2008) On the role of the first transmembrane domain in cation permeability and flux through the ATP-gated P2X2 receptor. Journal of Biological Chemistry. 283:5110-5117.
Samways, D.S.K. & Egan, T.M. (2007) Acidic amino acids impart enhanced Ca2+ permeabilities and fluxes in two members of the ATP-gated P2X receptor family. Journal of General Physiology. 129:245-256. PMCID: PMC2151611.
Egan, T.M., Samways, D.S.K. & Li, Z. (2006) Biophysics of P2X receptors. Pflüger’s Archives: European Journal of Physiology 452: 501-512.
Khakh, B.S.& Egan, T.M. (2005) Contribution of transmembrane regions to ATP-gated P2X2 channel permeability dynamics. Journal of Biological Chemistry. 280:6118-6129.
Li, Z., Samways, D.S.K., Migita, K., Voigt, M.M. & Egan, T.M. (2004) Gain and loss of channel function by alanine-substitutions in the transmembrane segments of the ATP-gated P2X2 receptors. Journal of Neuroscience. 24:7378-7386.
Dr. Egan is supported by grants from the NIH.
Honors and Awards
1984 Sigma Xi Research Honor Society, MIT Chapter
1986 – 1990 NIH NRSA Postdoctoral Fellowship
1990 – 1992 Cystic Fibrosis Foundation Postdoctoral Fellowship
2000 – 2003 American Heart Association Established Investigator Award2004 Life Elector, Clare Hall, University of Cambridge, UK
Professional Organizations and Associations
2009 Editorial Board, Journal of Experimental Pharmacology
2010 – 2016 NIH BPNS Biophysics of Neural Systems, regular member