The Faculty

Focus

Structure-function relation in voltage dependent membrane proteins

Biography

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.

Honors

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

Research Interests

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.

Select Papers

  1. Armstrong, C.M. and F. Bezanilla (1973). Currents related to movement of the gating particles of the sodium channels. Nature 242:459-461. 
  2. Cha, A. and F. Bezanilla (1997) Characterizing Voltage-dependent Conformational Changes in The Shaker K+ channel with fluorescence. Neuron 19:1127-1140.
  3. Cha, A. and F. Bezanilla. (1998). Structural implications of fluorescence quenching in the Shaker K+ channel.        J. Gen Physiol. 112:391-408. PMCID: 2229426
  4. Chanda, B. and F. Bezanilla. (2002). Tracking voltage-dependent conformational changes in skeletal muscle sodium channel during activation. J. Gen. Physiol. 120: 629-645. PMCID: 2229551
  5. Chanda, B., Asamoah, O.K, and F. Bezanilla  (2004) Coupling interactions between voltage sensors of the sodium channel as revealed by site-specific measurements. J. Gen. Physiol. 123: 217-230.PMCID: 2217449
  6. Chanda, B., O.K.Asamoah, R. Blunck, B. Roux and F. Bezanilla (2005) Gating charge displacement in voltage-gated channels involves limited transmembrane movement. Nature 436: 852-856.
  7. Sandtner, W., F. Bezanilla, and A. M. Correa  (2007) In Vivo Measurement of Intramolecular Distances Using Genetically Encoded Reporters. Biophys. J. 93: L45-L47. PMCID: 2025654
  8. Blunck, R., H. McGuire, H. C. Hyde and  F. Bezanilla. (2008) Fluorescence detection of the movement of single KcsA subunits reveals cooperativity. PNAS 105:20263-20268. PMCID: 2629256
  9. Villalba-Galea, C.A, W. Sandtner, D. M. Starace and F. Bezanilla (2008) S4-based Voltage Sensors have three major conformations. PNAS 105:17600-17607. PMID: 1881830. PMCID: 2584729
  10. Miceli F, Vargas E, Bezanilla F, Taglialatela M. (2012) Gating currents from Kv7 channels carrying neuronal hyperexcitability mutations in the voltage-sensing domain. Biophys J. 102(6):1372-82. PMC3309409
  11. Lacroix, J.J. and F. Bezanilla (2011) Control of a final gating charge transition by a hydrophobic residue in the S2 segment of a K+ channel voltage sensor . PNAS 108:6444-6449.PMCID: 3081032
  12. Vargas E, Bezanilla F, Roux B. (2011) In search of a consensus model of the resting state of a voltage-sensing domain. Neuron. 72(5):713-20. PMC:3268064
  13. Lacroix, J.J. and F. Bezanilla  (2012) Tuning the Voltage-Sensor Motion with a Single Residue. Biophys J. 103, L23-L25. . PMCID: 3414891
  14. Hyde, HC, Sandtner, W, Vargas, E, Dagcan, AT, Robertson, JL, Roux, B, Correa, AM & Bezanilla, F (2012) Nano-Positioning System for Structural Analysis of Functional Homomeric Proteins in Multiple Conformations. Structure 20, 1629–1640. PMC3633233
  15. 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