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Structure-function relation in voltage dependent membrane proteins
Catholic University, Santiago, Chile, B.S. , 1964, Biology
Catholic University, Santiago, Chile, M.S., 1967, Biophysics
Catholic University, Santiago, Chile, Ph.D., 1968, Biophysics
Laboratory of Biophysics, NINCDS, NIH, Postdoc., 1969, Biophysics
Dept. of Physiol., Univ. of Rochester, NY, Postdoc., 1969-71, Physiology
1964-1968, Instructor in Physics, School of Medicine, Catholic University, Chile.
1965-1969, Instructor, Laboratory of Neurophysiology, Catholic University, Chile.
1969, Postdoctoral Fellow (Biophysics), Laboratory of Biophysics, NINCDS, NIH, Bethesda, MD
1969-1971, Postdoctoral Fellow, Department of Physiology, University of Rochester, N.Y.
1972-1974, Assistant Professor, Department of Biology, Faculty of Sciences, University of Chile
1974, Research Associate, Department of Physiology, University of Rochester School of Medicine
1974-1977, Professor, Department of Biology, Faculty of Sciences, University of Chile
1975-1976, Visiting Assistant Professor, Dept. of Physiol., Univ. of Pennsylvania School of Medicine
1977-2005, Professor of Neuroscience, Department of Physiology, UCLA
2006-, Professor, Institute for Molecular Pediatric Sciences and Dept. of Biochemistry and Molecular Biology, University of Chicago.
1968-1969, Chilean Council for Scientific Research
1969, Visiting Fellow, NIH
1969-1971, Fellow Rockefeller Foundation
1977, Professor Rosenblueth Lecturer (I.P.N., Mexico)
1984-1986, Executive Committee, Biophysical Society
1985-1987, Council Member, Society of General Physiologists
1986-1987, Secretary of SOBLA
1990, Keneth S. Cole Award
1990, Society of General Physiologists Plenary Lecturer
1992, The Third Magoun Lecture, Brain Research Institute, UCLA
1998, Appointed as Leslie Scholar in Neuroscience
1994, American Physiological Society Annual Lecturer
1995, Appointed as Susumu Hagiwara Professor of Neuroscience
1999, Fellow of the Biophysical Society
2000, Annual Review Prize Lecture, The Physiological Society, U.K.
2002, Elected to the Latin American Academy of Sciences
2006, Elected to United States Academy of Sciences
2007, Doctor Honoris Causa University of Antwerp, Belgium &A.R. Martin Lecture
2008, Lillian Eichelber Cannon Professor
In voltage dependent channels, the electrical expression of their function is the ionic current which can be studied at the macroscopic level (the ionic current) and at the microscopic level (the single channel recording). But in addition to the ionic current, in these molecules the rearrangement of internal dipoles and charged groups under the influence of the external electric field produce gating currents. These currents are a direct expression of molecular rearrangements relevant to the operation (or gating) of the channel molecule.
With the advent of molecular cloning techniques, we have been able to carry out these studies with a detail not possible before by recording gating currents of cloned Shaker K+ and Sodium channels and describing their electrical properties with high resolution. Thus, we can modify the molecule to probe the role of specific amino acids in the voltage dependence and charge movement of the channel.
The main interest in the lab is the search for the dynamics of the molecular correlates of the function in membrane transport proteins. This is being approached with physical techniques such as temperature effects and complex capacitance measurements in the frequency domain combined with mutations of the molecule and assessed by gating currents, macroscopic currents and single molecule recordings. The correlation with structural changes are being monitored with optical techniques using real time fluorescence spectroscopy including lifetimes, changes in intensity and fluorescence resonance energy transfer from probes attached to strategic sites in the molecule of interest while being functional in the membrane.
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- Ruscic KJ, Miceli F, Villalba-Galea CA, Dai H, Mishina Y, Bezanilla F, Goldstein SA. (2013) IKs channels open slowly because KCNE1 accessory subunits slow the movement of S4 voltage sensors in KCNQ1 pore-forming subunits. Proc Natl Acad Sci U S A. 110(7):E559-66 PMCID: PMC3574954