I was a graduate student at the University of Wisconsin-Madison with Dr. Gail Robertson from 1993-1998. While there I characterized the molecular and biophysical properties of a voltage-gated ion channel (HERG) that plays a role in repolarization of the cardiac action potential. Mutations in this potassium channel gene are associated with an inherited cardiac arrhythmia (the Long QT syndrome). I was a postdoctoral fellow with Dr. Bill Zagotta at the University of Washington and Howard Hughes Medical Institute in Seattle from 1998 to 2004. My work there focused on the molecular physiology of cyclic nucleotide-gated (CNG) ion channels and their role in an inherited form of vision loss (retinitis pigmentosa) and the mechanism of their modulation by Ca2+-calmodulin. I joined the Department of Physiology as an Assistant Professor in 2004.
Ion channels are integral membrane proteins that control the electrical properties that underlie signaling in the nervous system. Ion channels respond to a wide variety of stimuli, including temperature, mechanical force, transmembrane voltage and chemical messengers. Upon activation, channels undergo conformational changes that control the passage of ions through the channel pore and across the cell membrane, which in turn controls membrane voltage and ultimately neuronal signaling. In this way, channels transduce local sensory and electrochemical input into the electrical signals used by the nervous system. Detailed understanding of the basic properties of ion channels, including the molecular rearrangements associated with channel opening and closing, the rearrangements resulting from the actions of modulatory factors and the steps controlling channel density at the cell surface are necessary to understand the electrical properties of cells. In addition, such understanding lends insight into how inherited defects in channel genes result in disease states. To these ends, my lab investigates the molecular specializations underlying ion channel function in potassium channels activated by voltage and cation channels activated by intracellular cyclic nucleotides. The lab employs a variety of techniques to explore these questions including molecular biology, biochemistry, electrophysiology and fluorescence-based imaging.
Research ImagesBright field image of a pipette tip with an excised membrane patch containing cyclic nucleotide-gated channels
Fluorescence image after addition of fluorescently labeled Ca2+-calmodulin to the inner face of the patch pipette. From Trudeau and Zagotta, Journal of General Physiology, 2004
Trudeau, M.C., Warmke, J.W., Ganetzky, B. and Robertson, G.A. (1995) HERG, a human inward rectifier in the voltage-gated potassium channel family. Science. 269, 92-95.
Trudeau, M.C., Titus, S.A., Branchaw, J.L., Ganetzky, B. and Robertson, G.A. (1999) Functional analysis of a mouse brain Elk-type K+ channel. Journal of Neuroscience. 19, 2906-2918.
Trudeau, M.C. and Zagotta, W.N. (2002) An intersubunit interaction regulates trafficking of rod cyclic nucleotide-gated channels and is disrupted in an inherited form of blindness. Neuron. 34, 197-207.
Trudeau, M.C. and Zagotta, W.N. (2002) Mechanism of calcium/calmodulin inhibition of rod cyclic nucleotide-gated channels. Proc. Natl. Acad. Sci. USA, 99(12), 8424-8429.
Trudeau, M.C. and Zagotta, W.N. (2003) Calcium/calmodulin modulation of olfactory and rod cyclic nucleotide-gated ion channels. Journal of Biological Chemistry. 278, 18705-18708.
Trudeau, M.C. and Zagotta, W.N. (2004) Dynamics of Ca2+-calmodulin dependent inhibition of rod cyclic nucleotide-gated channels measured by patch-clamp fluorometry. Journal of General Physiology. 124(3), 211-223. PMCID: PMC2233886
Shepard P.D. and Trudeau, M.C. Emerging roles for ether á go-go related gene potassium channels in the brain. Journal of Physiology, Oct 15;586 (Pt 20):4785-6. 2008. PMCID: PMC2614064
Gustina, A.S. and Trudeau, M.C. A recombinant N-terminal domain fully restores deactivation gating in N-truncated and long QT syndrome mutant hERG potassium channels. Proceedings of the National Academy of Sciences. 106:13082-13087. 2009. PMCID: PMC2722319
Gustina, A.S. and Trudeau, M.C. hERG potassium channel gating is mediated by N- and C-terminal region interactions. Journal of General Physiology, 137, 315-325. 2011. PMCID: PMC3047612
Gianulis, E.C. and Trudeau, M.C. Rescue of aberrant gating by a genetically-encoded PAS domain in several long QT syndrome mutant human ether á go-go related gene potassium channels. Journal of Biological Chemistry, 286, 22160-22169. 2011. PMCID: PMC3121360
Trudeau, M.C., Leung, L.M., Roti Roti, E., and Robertson, G.A. hERG1a N-terminal eag domain-containing polypeptides regulate homomeric hERG1b and heteromeric hERG1a/hERG1b channels: A possible mechanism for Long QT syndrome. Journal of General Physiology, 138(6), 581-592. 2011. PMCID: PMC3226966
Gustina, A.S. and Trudeau, M.C. hERG Potassium Channel Regulation by the N-terminal eag domain. Cellular Signalling, 2012.