Gail A. Robertson

 

 

Molecular Mechanisms of Ion Channel Function and Disease

E-mail: robertson@physiology.wisc.edu

Research Strengths: Membrane Excitability and Synaptic Transmission, Molecular Neuroscience, Neurobiology of Disease

We are interested in the molecular basis of membrane excitability and its role in disease in the human heart and brain. At the focus of our studies is HERG, a potassium channel that helps repolarize the cardiac action potential. Disruption of HERG channels by inherited mutations or drug block causes a life-threatening condition known as Long QT Syndrome (LQTS), a leading cause of sudden cardiac death. We are interested in how the biophysical mechanisms of gating enable HERG to fulfill its normal physiological role in the heart, and how disruption of HERG leads to disease. We are using genetic, biochemical and electrophysiological means to identify proteins that interact with HERG and facilitate the biogenesis and transport of the channels to the membrane. These newly-discovered proteins may also be novel disease targets for LQTS. In addition, ongoing efforts are aimed at uncovering the functional role of HERG in the brain, where it was first identified.

Selected Publications:

• Robertson, G.A., E.M.C. Jones, and J. Wang. 2005. Gating and assembly of heteromeric hERG1a/1b channels underlying IKr in the heart. Novartis Foundation Symposium 266: 4-15. [PDF]
• Jones, E.M.C., E.C. Roti Roti, J. Wang, S.A. Delfosse, and G.A. Robertson. 2004. Cardiac IKr channels minimally comprise hERG 1a and 1b subunits. J. Biol. Chem. 279: 44690-44694. [PDF]
• Roti Roti, E.C., C.D. Myers, R.A. Ayers, D.E. Boatman, S.A. Delfosse, E.K. Chan, M.J. Ackerman, C.T. January, and G.A. Robertson. 2002. Interaction with GM130 during HERG ion channel trafficking. Disruption by type 2 congenital long QT syndrome mutations. J. Bio. Chem. 277: 47779-47785. [PDF]
• Robertson, G.A. 2000. LQT2: Amplitude reduction and loss of selectivity in the tail that wags the HERG channel. Circ. Res. 86: 492-493. [PDF]
• Wang, J., C.D. Myers, and G.A. Robertson. 2000. Dynamic regulation of slow deactivation by an amino terminal peptide in HERG channels. J. Gen. Physiol. 115: 749-758. [PDF]
• Trudeau, M.C., S.A. Titus, J.L. Branchaw, B. Ganetzky, and G.A. Robertson. 1999. Functional analysis of a mouse Elk-type K+ channel. J. Neurosci. 19: 2906-2918. [PDF]
• Herzberg*, I.M., Trudeau*, M.C., and G.A. Robertson. 1998. Transfer of rapid inactivation and E-4031 sensitivity from HERG to M-EAG Channels. J. Physiol. 511.1: 3-14. (*Designates co-first authors.) [PDF]
• Wang, J., M.C. Trudeau, A. Zappia, and G.A. Robertson. 1998. Regulation of deactivation by an amino terminal domain in HERG potassium channels. J. Gen. Physiol. 112: 637-647. [PDF]