Arthur Karlin, PhD
- Higgins Professor of Biochemistry and Molecular Biophysics
- Professor of Neurology
- Professor of Physiology & Cellular Biophysics
- Director, Center for Molecular Recognition
Born January 14, 1936, Philadelphia, PA. Attended Central High School, 1949-1953, Swarthmore College, 1953 - 1957, BA, major Mathematics, and Rockefeller University, 1957 - 1962, PhD. Was a post-doctoral trainee in David Nachmansohn's group at the College of Physicians and Surgeons, 1962 - 1965. Started research on acetylcholinesterase and nicotinic acetylcholine receptor and continued working on the receptor for 40 years. More recently worked on the structure and function of potassium channels, mainly the BK calcium and voltage-activated potassium channel. Concurrently, developed a mathematical model of arterial smooth muscle function that successfully simulated the myogenic response and the responses to alpha and beta adrenergic agonists, nitric oxide, and endothelial relaxing factor. For about 20 years until the present, taught one quarter of the Molecular Biophysics course and a semester course in Membrane Receptors and Transport Proteins. From 1985 to 1989, director of the Summer Course in Neurobiology at the Marine Biological Laboratory, Woods Hole, MA. Married to Cynthia Rollings, Children: Oliver, Abigail, Daniel, Samuel, Joe and Emma.
1962-1963: Research Assistant, College of Physicians & Surgeons, Columbia University
1963-1964: Research Associate, College of Physicians & Surgeons, Columbia University
1965-1969: Assistant Professor of Neurology, P & S, Columbia University
1969-1974: Associate Professor of Physiology in Neurology, P & S, Columbia University
1974-1978: Associate Professor of Neurochemistry, P & S, Columbia University
1978-present: Professor of Biochemistry and Molecular Biophysics, and Neurology
1989-present: Higgins Professor of Biochemistry and Molecular Biophysics, and Neurology, and Director of the Center for Molecular Recognition, P & S, Columbia University
1991- present: Professor of Physiology and Cellular Biophysics, P & S, Columbia University.
Credentials & Experience
Education & Training
- PhD, 1962 Biochemistry & Physiology, Rockefeller University
- Fellowship: 1964 Columbia University College of Physicians and Surgeons
Honors & Awards
1975: Lucy G. Moses Prize in Basic Neurology; 1979
1984: Grass Traveling Scientist, Vanderbilt University
1984: J. H. Quastel Visiting Professor, McGill University
1985: John C. Krantz, Jr. Lectureship in Pharmacology and Experimental Therapeutics, U. Md.
1985: The Louis and Bert Freedman Foundation Award for Research in Biochemistry, NYAS
1987: Javits Neuroscience Investigator Award
1989: Fellow of the American Association for the Advancement of Science
1989: Stevens Triennial Prize, College of Physicians and Surgeons
1989: Harvey Society Lecturer
1990: Dean's Distinguished Lecturer in the Basic Sciences
1994: Fellow of the American Academy of Arts and Sciences
1999: Member of the National Academy of Sciences
2004: Noun Shavit Lecturer, Ben Gurion University
Understanding the function of molecular receptors has been my guiding interest and the central mission of the Center. Receptors function in three steps: signal recognition, transduction, and transmission. This is exemplified by the nicotinic acetylcholine receptors, on which I worked for forty years. These receptors bind acetylcholine, transduce this binding into the opening of a pore, and conduct cations causing a depolarization of the synaptic membrane. We identified the overall receptor structure and, within this, the specific sites and substructures at the front-line of these functional steps. More recently, this approach was applied to the BK channel, a voltage- and calcium-ion-activated channel, widely expressed and responsible for membrane hyperpolarization.
Also recently, I began to consider cellular functions that depend on circuits of signaling components. Cellular function depends on the functions of individual molecular components and on their coordination via direct or indirect interactions. Cellular function also depends on cellular structure and on the distribution of the functional molecular components in these structures. Crucial to the specificity and effectiveness of the interactions among functional components are microdomains, which both channel and amplify the signals between components. My approach to understanding such systems is to represent all steps as kinetic equations, consistent with thermodynamics, and to solve the resulting equations in time and space. To the extent that experimental data exist, the equations are fit to these data. Such a model is a mathematical summary of the known properties of the components and of the target cellular function. Notwithstanding, such a model is a hypothetical outline of how the cell might function, always wanting experimental tests and refinement.
- Biochemistry/Biophysics/Systems Biology/Receptors/Ion Channels/Transporters
BK CHANNEL MODULATION BY BETA SUBUNITS (Federal Gov)
Apr 1 2006 - Jan 31 2016
ALLOSTERIC MODULATION OF CARDIOVASCULAR ION CHANNELS (Federal Gov)
Sep 1 2007 - Apr 30 2013
Karlin A (2015) Membrane potential and Ca2+ concentration dependence on pressure and vasoactive agents in arterial smooth muscle: A model. J. Gen. Physiol. 146:79–96 www.jgp.org/cgi/doi/10.1085/jgp.201511380.
Liu G, Zakharov SI, Yao Y, Marx SO, and Karlin, A (2015) Positions of the cytoplasmic end of BK alpha S0 helix relative to S1-S6 and of beta1 TM1 and TM2 relative to S0-S6. J Gen Physiol 145:185-199. doi:10.1085/jgp.201411337.
Niu X, Liu G, Wu RS, Chudasama N, Zakharov SI, et al. (2013) Orientations and proximities of the extracellular ends of transmembrane helices S0 and S4 in open and closed BK potassium channels. PLoS ONE 8(3): e58335. doi:10.1371/journal.pone.0058335.
Chan, P.J., Osteen, J.D., Xiong, D., Bohnen, M.S., Doshi, D., Sampson, K.J., Marx, S.O., Karlin, A., and Kass, R.S. (2012) Characterization of KCNQ1 atrial fibrillation mutations reveals distinct dependence on KCNE1. J. Gen Physiol. 139:135-144.
Liu, G., Niu, X., Wu, R.S., Chudasama, N., Yao, Y., Jin, X., Weinberg, R., Zakharov, S.I., Motoike, H., Marx, S.O., and Karlin, A. (2010) Location of modulatory subunits in BK potassium channels. J. Gen. Physiol. 135:449-459.
Wu, R.S., Chudasama, N., Zakharov, S.I., Doshi, D., Motoike, H., Liu, G., Yao, Y., Niu, X., Deng, S.-X., Landry, D.W., Karlin, A., and Marx, S.O. (2009) Location of the beta 4 transmembrane helices in the BK potassium channel. J. Neurosci. 29:8321-8328.
Chung, D.Y., Chan, P. J., Bankston, J.R., Yang, L., Liu, G., Marx, S.O., Karlin, A., Kass, R.S. (2008) Location of KCNE1 relative to KCNQ1 in the IKS potassium channel by disulfide crosslinking of substituted cysteines. Proc. Natl. Acad. Sci. USA 106:743-748.
Liu, G., Zakharov, S., Yang., L., Wu, R., Deng, S., Landry, D., Karlin, A., Marx, S. (2008) Locations of the beta1 transmembrane helices in the BK potassium channel. Proc. Natl. Acad. Sci. USA 105:10727-10732.
Liu, G., Zakharov, S., Yang., L., Deng, S., Landry, D., Karlin, A., Marx, S. (2008) Position and role of the BK channel subunit S0 helix inferred from disulfide crosslinking. J. Gen. Physiol 131: 537-548.
Li, Y., Karlin, A., Loike, J.D., and Silverstein, S. C. (2004) A critical concentration of neutrophils required to block growth of Staphylococcus epidermidis in fibrin gels and of E. coli in rabbit dermis. J. Exp. Med.200:613-622.
Li, J.,Shi, L., and Karlin, A. (2003) A photochemical approach to the lipidaccessibility of engineered cysteinyl residues. Proc. Natl. Acad. Sci. USA 100: 886-891.
Yu, Y., Shi, L., and Karlin, A. (2003). Structural effects of quinacrine binding in the open channel of theacetylcholine receptor. Proc. Natl. Acad. Sci. USA 100: 3907-3912.
Karlin, A. (2003) Nicotinic acetylcholine receptors: Probing functionally significant structural changes with site directed reactions. In “Cholinergic Mechanisms: Function and Dysfunction”, A. Fisher and H. Soreq, eds, chapter 2.
Karlin, A. (2002). Emerging structure of the nicotinic acetylcholine receptors. Nature Rev. Neurosci. 3: 102-114.
Li,J., Xu, Q., Cortes, D. M., Perozo, E., Laskey, A., and Karlin, A.(2002) Reactions of cysteines substituted in the amphipathic N-terminaltail of a bacterial potassium channel with hydrophilic and hydrophobicmaleimides. Proc. Natl. Acad. Sci. USA 99: 11605-11610.
Wilson, G.G., and Karlin, A. (2001). Acetylcholine receptor channelstructure in the resting, open, and desensitized states probed with thesubstituted-cysteine-accessibility method. Proc. Natl. Acad. Sci. USA98: 1241-1248.