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Electrical excitability in the brain: voltage-gated ion
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channels, cell & circuit function, neural control of behavior,
relationship between spike activity and neuronal viability.
Electrical activity underlies most aspects of brain function.
Our research focuses on the voltage-gated ion channels that
confer electrical excitability on neurons and the consequences of
changes in channel activity for neuronal firing, circuit function,
behavior, and neuronal viability during development and aging.
People
Projects
Publications
Work in our lab spans many levels of analysis, from the
molecular to the behavioral. We are studying how voltage controls
the activity of K+ channels, how changes in channel function or
expression affect the firing patterns of neurons and the emergent
properties of neuronal circuits, and how altering neuronal
excitability affects behavior. We are also investigating the
relationship between excitability and neuronal survival at different
stages of life.
We use a wide variety of experimental approaches to address
these issues, including electrophysiology, imaging, biochemistry,
molecular biology, genetics, and behavioral analysis. In the past
few years, we have adopted the zebrafish, Danio rerio, as our main
model system for integrative analysis. We also use Xenopus
oocytes to investigate channel function and primary cultures of
rodent neurons to explore the relationship between channel
activity and neuronal function and viability.
Contact
Positions
Map & Directions
We are always looking for bright, hard-working individuals who
want to work in a collaborative environment focusing on
mechanistic, quantitative approaches to key questions in
neuroscience.
Links
Electrical activity underlies most aspects of brain function.
Our research focuses on the voltage-gated ion channels that
confer electrical excitability on neurons and the consequences of
changes in channel activity for neuronal firing, circuit function,
behavior, and neuronal viability during development and aging.
Work in our lab spans many levels of analysis, from the
molecular to the behavioral. We are studying how voltage controls
the activity of K+ channels, how changes in channel function or
expression affect the firing patterns of neurons and the emergent
properties of neuronal circuits, and how altering neuronal
excitability affects behavior. We are also investigating the
relationship between excitability and neuronal survival at different
stages of life.
We use a wide variety of experimental approaches to address
these issues, including electrophysiology, imaging, biochemistry,
molecular biology, genetics, and behavioral analysis. In the past
few years, we have adopted the zebrafish, Danio rerio, as our main
model system for integrative analysis. We also use Xenopus
oocytes to investigate channel function and primary cultures of
rodent neurons to explore the relationship between channel
activity and neuronal function and viability.
We are always looking for bright, hard-working individuals who
want to work in a collaborative environment focusing on
mechanistic, quantitative approaches to key questions in
neuroscience.
People
Home
Projects
Publications
Diane M Papazian PhD
Professor
Department of Physiology
UCLA
Current Lab Members
Jie Yi (Ray) Hsieh
Fadi (Pete) Issa
Contact
Meng-chin Lin
Natali Minassian
Positions
Allan Mock
Liz Vuong
Map & Directions
Links
Lab Photos
Former Lab Members
Chih-Yung Tang, National Taiwan University
Seema Tiwari-Woodruff, UCLA
Lucia Santacruz-Toloza, Duke University
Christine Schulteis, Immusol
Will Silverman, University of Miami
Muriel Lainé, University of Chicago
John Bannister, University of Tennessee
Chris Mazzochi
Jessica Richardson, UC Davis School of Law
Myong-chul Koag
Mike Myers, Cal State Long Beach
Raj Khanna, Indiana University
Naomi Nagaya, University of Michigan
Yu Huang, Chinese University of Hong Kong
Scott John, UCLA
Max Shao, UCLA
Sang-Ah Seoh
Miriam Pillos
Diane M Papazian PhD
Professor
Department of Physiology
UCLA
Education: 1973-1977 B.S. (Chemistry), with high distinction
University of Michigan
Ann Arbor, Michigan
1977-1983 Ph.D. (Biological Chemistry)
Harvard University
Cambridge, Massachusetts
Professional Positions: 1983-1989 Postdoctoral Fellow
Laboratory of Lily and Yuh Nung Jan
University of California, San Francisco
1989-1994 Assistant Professor, Department of Physiology
UCLA School of Medicine
1994-2000 Associate Professor, Department of Physiology
UCLA School of Medicine
1999-2005 Executive Vice Chair, Department of Physiology
UCLA David Geffen School of Medicine
2000-now Professor, Department of Physiology
UCLA David Geffen School of Medicine
Honors:
Fellow of the Biophysical Society, 2009
H. W. Magoun Distinguished Lecturer, UCLA Brain Research Institute, 2008
Contributing Member, Faculty of 1000, 2004-2007
Councilor, Biophysical Society, 2004-2006
Fellow, American Association for the Advancement of Science, 1999
Grass Foundation Traveling Scientist, Society for Neuroscience, 1997
Pew Scholar in the Biomedical Sciences, 1991-1995
Klingenstein Fellow in the Neurosciences, 1989-1992
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Jie Yi (Ray) Hsieh
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Fadi (Pete) Issa PhD
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Meng-chin A Lin PhD
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Natali A Minassian
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Allan Mock
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Papazian Lab Photos
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Projects
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Gating of voltage-dependent K+ channels (more . . .)
We are investigating the mechanism of voltage-dependent activation in K+
channels. K+ channels are tetramers with a central K+-selective pore and 4
voltage sensor domains, one per subunit. Upon membrane depolarization,
the voltage sensor domains undergo conformational changes that result in
pore opening. Our current goals are to identify experimental constraints
that make it possible to model the structure of the closed channel and to
determine the pathway taken by the S4 segment, the main moving
element in the voltage sensor, during activation.
Neuronal Excitability and Spinocerebellar Ataxia Type 13 (more . . .)
Publications
Contact
Positions
Spinocerebellar Ataxia Type 13 is an autosomal dominant genetic disease in humans caused by
mutations in KCNC3, which encodes Kv3.3, a voltage-gated K+ channel. The two original SCA13
mutations are associated with distinct clinical manifestations. A mutation in the voltage sensor domain
leads to progressive adult onset ataxia accompanied by degeneration of cerebellar neurons. This
mutant subunit has a strong dominant negative effect on Kv3 expression. In contrast, a mutation in the
pore domain causes a form of SCA13 that emerges in infancy, characterized by a severely shrunken and
malformed cerebellum and non-progressive motor deficits. This mutation affects gating, shifting the
voltage dependence of activation in the negative direction and dramatically slowing channel closing.
We are testing the hypothesis that changes in Kv3.3 channel function alter the excitability of cerebellar
neurons, with detrimental consequences for motor behavior and neuronal survival during brain
development or aging. We are working to determine how changes in excitability decrease the viability
of neurons and why different mutations affect neuronal survival at different stages of life.
Zebrafish Model of Human Ataxia (more . . .)
We are expressing SCA13 mutant subunits in zebrafish to determine the consequences for neuronal
function, development, viability, and locomotor behavior. Currently, we are focusing on the spinal cord.
Map & Directions Endogenous Kv3.3 is expressed in primary motor neurons, which control the fastest and largest
amplitude movements in zebrafish, including the startle (escape) response. Expression of a dominant
negative SCA13 subunit dramatically affects the escape response, reducing the precision and amplitude
of the C start and impairing the execution of subsequent steps in the motor program. These features
strongly resemble human ataxia.
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Selected Recent Publications
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People
Projects
Silverman, W.R., Roux, B., and Papazian, D.M. (2003) Structural basis of two-stage voltage-dependent activation in K+
channels. Proc. Natl. Acad. Sci. USA 100, 2935-2940.
Contact
Positions
Lainé, M., Lin, M.A., Bannister, J.P.A., Silverman, W.R., Mock, A.F., Roux, B., and Papazian, D.M. (2003) Atomic
proximity between S4 segment and pore domain in Shaker potassium channels. Neuron 39, 467-481.
Tiwari-Woodruff, S.K.*, Lin, M.A.*, Schulteis, C.T., and Papazian, D.M. (2000) Voltage-dependent structural
interactions in the Shaker K+ channel. J. Gen. Physiol. 115, 123-138. (Cover article) (*co-first authors)
Silverman, W.R., Tang, C.-Y., Mock, A.F., Huh, K.-B., and Papazian, D.M. (2000) Mg2+ modulates voltage-dependent
activation in ether-à-go-go potassium channels by binding between transmembrane segments S2 and S3. J. Gen.
Physiol. 116, 663-677.
Map & Directions
Links
Tang, C.-Y., Bezanilla, F., and Papazian, D.M. (2000) Extracellular Mg2+ modulates slow gating transitions and the
opening of Drosophila ether-à-go-go potassium channels. J. Gen. Physiol. 115, 319-337.
Full Publication List (PubMed)
Lin, M.A., Abramson, J., and Papazian, D.M. (2009) Transfer of ion binding site from ether-à-go-go to Shaker: Mg2+ binds to resting
state to modulate channel opening. Submitted for publication.
Figueroa, K.P.*, Minassian, N.A.*, Stevanin G., Waters, M., Garibyan, V., Bürk, K., Brice, A., Dürr, A., Papazian, D.M., and Pulst, S.M.
(2009) SCA13: KCNC3 mutations and genotype/phenotype correlations in 260 familial ataxia patients. Hum. Mutat., in press. (*cofirst authors)
Koag, M.C. and Papazian, D.M. (2009) Voltage-dependent conformational changes of KvAP S4 segment in bacterial membrane
environment. Channels 3, epub ahead of print (PMID 19713752).
Lin, M.A. and Papazian, D.M. (2007) Differences between ion binding to eag and HERG voltage sensors contribute to differential
regulation of activation and deactivation gating. Channels 1, 429-437.
Waters, M.F., Minassian, N.A., Stevanin, G., Figueroa, K.P., Bannister, J.P.A., Nolte, D., Mock, A.F., Evidente, V.G., Fee, D., Müller, U.,
Dürr, A., Brice, A., Papazian, D.M., and Pulst, S.M. (2006) Mutations in the voltage-gated potassium channel KCNC3 cause
degenerative and developmental CNS phenotypes. Nat. Genet. 38, 447-451.
Bannister, J.P.A., Chanda, B., Bezanilla, F., and Papazian, D.M. (2005) Optical detection of rate-determining, ion-modulated
conformational changes of the ether-à-go-go K+ channel voltage sensor. Proc. Natl. Acad. Sci. USA 102, 18718-18723.
Silverman, W.R., Roux, B., and Papazian, D.M. (2003) Structural basis of two-stage voltage-dependent activation in K+ channels. Proc.
Natl. Acad. Sci. USA 100, 2935-2940.
Lainé, M., Lin, M.A., Bannister, J.P.A., Silverman, W.R., Mock, A.F., Roux, B., and Papazian, D.M. (2003) Atomic proximity between S4
segment and pore domain in Shaker potassium channels. Neuron 39, 467-481.
Tiwari-Woodruff, S.K.*, Lin, M.A.*, Schulteis, C.T., and Papazian, D.M. (2000) Voltage-dependent structural interactions in the Shaker
K+ channel. J. Gen. Physiol. 115, 123-138. (Cover article) (*co-first authors)
Silverman, W.R., Tang, C.-Y., Mock, A.F., Huh, K.-B., and Papazian, D.M. (2000) Mg2+ modulates voltage-dependent activation in
ether-à-go-go potassium channels by binding between transmembrane segments S2 and S3. J. Gen. Physiol. 116, 663-677.
Tang, C.-Y., Bezanilla, F., and Papazian, D.M. (2000) Extracellular Mg2+ modulates slow gating transitions and the opening of
Drosophila ether-à-go-go potassium channels. J. Gen. Physiol. 115, 319-337.
Figueroa, K.P.*, Minassian, N.A.*, Stevanin G., Waters, M., Garibyan, V., Bürk, K., Brice, A., Dürr, A., Papazian, D.M., and Pulst, S.M. (2009) SCA13:
KCNC3 mutations and genotype/phenotype correlations in 260 familial ataxia patients. Submitted for publication. (*co-first authors)
Lin, M.A., Abramson, J., and Papazian, D.M. (2009) Transfer of ion binding site from ether-à-go-go to Shaker: Mg2+ binds to resting state to
modulate channel opening. Submitted for publication.
Koag, M.C. and Papazian, D.M. (2009) Voltage-dependent conformational changes of KvAP S4 segment in bacterial membrane environment.
Channels 3, epub ahead of print (PMID 19713752).
Lin, M.A. and Papazian, D.M. (2007) Differences between ion binding to eag and HERG voltage sensors contribute to differential regulation of
activation and deactivation gating. Channels 1, 429-437.
Waters, M.F., Minassian, N.A., Stevanin, G., Figueroa, K.P., Bannister, J.P.A., Nolte, D., Mock, A.F., Evidente, V.G., Fee, D., Müller, U., Dürr, A., Brice,
A., Papazian, D.M., and Pulst, S.M. (2006) Mutations in the voltage-gated potassium channel KCNC3 cause degenerative and developmental CNS
phenotypes. Nat. Genet. 38, 447-451.
Bannister, J.P.A., Chanda, B., Bezanilla, F., and Papazian, D.M. (2005) Optical detection of rate-determining, ion-modulated conformational changes
of the ether-à-go-go K+ channel voltage sensor. Proc. Natl. Acad. Sci. USA 102, 18718-18723.
Silverman, W.R., Roux, B., and Papazian, D.M. (2003) Structural basis of two-stage voltage-dependent activation in K+ channels. Proc. Natl. Acad.
Sci. USA 100, 2935-2940.
Lainé, M., Lin, M.A., Bannister, J.P.A., Silverman, W.R., Mock, A.F., Roux, B., and Papazian, D.M. (2003) Atomic proximity between S4 segment and
pore domain in Shaker potassium channels. Neuron 39, 467-481.
Tiwari-Woodruff, S.K.*, Lin, M.A.*, Schulteis, C.T., and Papazian, D.M. (2000) Voltage-dependent structural interactions in the Shaker K+ channel. J.
Gen. Physiol. 115, 123-138. (Cover article) (*co-first authors)
Silverman, W.R., Tang, C.-Y., Mock, A.F., Huh, K.-B., and Papazian, D.M. (2000) Mg2+ modulates voltage-dependent activation in ether-à-go-go
potassium channels by binding between transmembrane segments S2 and S3. J. Gen. Physiol. 116, 663-677.
Tang, C.-Y., Bezanilla, F., and Papazian, D.M. (2000) Extracellular Mg2+ modulates slow gating transitions and the opening of Drosophila ether-à-gogo potassium channels. J. Gen. Physiol. 115, 319-337.
Figueroa, K.P.*, Minassian, N.A.*, Stevanin G., Waters, M., Garibyan, V., Bürk, K., Brice,
A., Dürr, A., Papazian, D.M., and Pulst, S.M. (2009) SCA13: KCNC3 mutations and
genotype/phenotype correlations in 260 familial ataxia patients. Submitted for
publication. (*co-first authors)
Lin, M.A., Abramson, J., and Papazian, D.M. (2009) Transfer of ion binding site from
ether-à-go-go to Shaker: Mg2+ binds to resting state to modulate channel opening.
Submitted for publication.
Koag, M.C. and Papazian, D.M. (2009) Voltage-dependent conformational changes of
KvAP S4 segment in bacterial membrane environment. Channels 3, epub ahead of print
(PMID 19713752).
Lin, M.A. and Papazian, D.M. (2007) Differences between ion binding to eag and HERG
voltage sensors contribute to differential regulation of activation and deactivation
gating. Channels 1, 429-437.
Waters, M.F., Minassian, N.A., Stevanin, G., Figueroa, K.P., Bannister, J.P.A., Nolte, D.,
Mock, A.F., Evidente, V.G., Fee, D., Müller, U., Dürr, A., Brice, A., Papazian, D.M., and
Pulst, S.M. (2006) Mutations in the voltage-gated potassium channel KCNC3 cause
degenerative and developmental CNS phenotypes. Nat. Genet. 38, 447-451.
Bannister, J.P.A., Chanda, B., Bezanilla, F., and Papazian, D.M. (2005) Optical detection
of rate-determining, ion-modulated conformational changes of the ether-à-go-go K+
channel voltage sensor. Proc. Natl. Acad. Sci. USA 102, 18718-18723.
Figueroa, K.P.*, Minassian, N.A.*, Stevanin G., Waters, M., Garibyan, V., Bürk, K., Brice, A., Dürr, A., Papazian, D.M., and Pulst, S.M. (2009) SCA13:
KCNC3 mutations and genotype/phenotype correlations in 260 familial ataxia patients. Submitted for publication. (*co-first authors)
Lin, M.A., Abramson, J., and Papazian, D.M. (2009) Transfer of ion binding site from ether-à-go-go to Shaker: Mg2+ binds to resting state to
modulate channel opening. Submitted for publication.
Koag, M.C. and Papazian, D.M. (2009) Voltage-dependent conformational changes of KvAP S4 segment in bacterial membrane environment.
Channels 3, epub ahead of print (PMID 19713752).
Lin, M.A. and Papazian, D.M. (2007) Differences between ion binding to eag and HERG voltage sensors contribute to differential regulation of
activation and deactivation gating. Channels 1, 429-437.
Waters, M.F., Minassian, N.A., Stevanin, G., Figueroa, K.P., Bannister, J.P.A., Nolte, D., Mock, A.F., Evidente, V.G., Fee, D., Müller, U., Dürr, A., Brice,
A., Papazian, D.M., and Pulst, S.M. (2006) Mutations in the voltage-gated potassium channel KCNC3 cause degenerative and developmental CNS
phenotypes. Nat. Genet. 38, 447-451.
Bannister, J.P.A., Chanda, B., Bezanilla, F., and Papazian, D.M. (2005) Optical detection of rate-determining, ion-modulated conformational changes
of the ether-à-go-go K+ channel voltage sensor. Proc. Natl. Acad. Sci. USA 102, 18718-18723.
Silverman, W.R., Roux, B., and Papazian, D.M. (2003) Structural basis of two-stage voltage-dependent activation in K+ channels. Proc. Natl. Acad.
Sci. USA 100, 2935-2940.
Lainé, M., Lin, M.A., Bannister, J.P.A., Silverman, W.R., Mock, A.F., Roux, B., and Papazian, D.M. (2003) Atomic proximity between S4 segment and
pore domain in Shaker potassium channels. Neuron 39, 467-481.
Tiwari-Woodruff, S.K.*, Lin, M.A.*, Schulteis, C.T., and Papazian, D.M. (2000) Voltage-dependent structural interactions in the Shaker K+ channel. J.
Gen. Physiol. 115, 123-138. (Cover article) (*co-first authors)
Silverman, W.R., Tang, C.-Y., Mock, A.F., Huh, K.-B., and Papazian, D.M. (2000) Mg2+ modulates voltage-dependent activation in ether-à-go-go
potassium channels by binding between transmembrane segments S2 and S3. J. Gen. Physiol. 116, 663-677.
Tang, C.-Y., Bezanilla, F., and Papazian, D.M. (2000) Extracellular Mg2+ modulates slow gating transitions and the opening of Drosophila ether-à-gogo potassium channels. J. Gen. Physiol. 115, 319-337.
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Contact Information
Diane M Papazian PhD
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Positions
E-mail: [email protected]
Phone: (310) 206-7043
Lab: (310) 825-5766
Fax: (310) 206-5661
U.S. Mailing Address:
Shipping Address:
Department of Physiology
David Geffen School of Medicine at UCLA
650 Charles Young Drive South
Box 915751, Room 53-231 CHS
Los Angeles, CA 90095-1751
Medical Receiving
UCLA Physiology
650 Charles Young Drive South
Box 915751, Room 53-231 CHS
Los Angeles, CA 90095-1751
Campus Address:
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Department of Physiology
53-159 CHS
Mail code 175118
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Graduate Students
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Prospective graduate students have the
option of applying to UCLA Access or
directly to the Indepartmental PhD
Programs in Neuroscience or in Molecular,
Cellular and Integrative Physiology.
Postdoctoral Fellows
Recent PhD recipients with training relevant to our research are
invited to apply. Please send your CV and the names of three
references to Diane Papazian. At this time, only postdoc candidates
who have or can raise their own salary support are being considered.
Staff Research Positions
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We occasionally have open positions for Staff Research Associates.
These jobs are posted at: (URL)
Research Experiences for Undergraduates
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Motivated undergraduates who are interested in specific projects in
the lab should contact Diane Papazian. Only undergraduates who will
commit to spending a minimum of 15 hours per week at the bench will
be considered.
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Map & Directions
From the 405, exit on Wilshire Blvd heading
east. Turn left on Westwood Blvd and follow it
onto campus. Turn right at Charles Young Dr.
South. You can enter The Center for Health
Sciences through the School of Public Health on
the south side of the block ( ). We are on the
5th floor, 53-159 CHS.
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