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Research Area: Cardiovascular Physiology
Ion
channels and membrane transporters are key determinants of the initiation
and conduction of the cardiac impulse. Moreover, alterations in the
function of these membrane proteins due to genetic mutation, disease or
drugs can alter their function leading to abnormal cardiac rhythms.
The work in my laboratory has been focused on attaining an understanding of
ion channel function and localization on one hand and the initiation of
complex cardiac rhythms on the other. We are using molecular methods,
including yeast two-hybrid screens, and confocal microscopy with
immunohistochemistry to identify protein interaction and localization. Using
electrophysiological methods, including patch clamp techniques, we determine
the functional expression and biophysical properties of channels in
heterologous cells and isolated cardiac myocytes. In order to understand the
genesis of cardiac rhythms we use optical dyes and a cooled CCD camera
system or photodiodes to image the conduction of the cardiac impulse in
cultured cardiac myocytes or cardiac tissue. The rhythms generated are
analyzed and modeled using nonlinear mathematical techniques. The above
approaches are used to study the changes that occur with development,
cardiac arrhythmias and disease states, such as cardiac ischemia.
Education: B.Sc., Concordia,
Ph.D., Dalhousie
Walker VE, Atanasiu R, Lam H, Shrier A.
Co-chaperone FKBP38 promotes HERG trafficking.
J Biol Chem. 2007 282(32):23509-16.
Han W, Nattel S, Noguchi T, Shrier A.
C-terminal
domain of Kv4.2 and associated KChIP2 interactions regulate functional
expression and gating of Kv4.2.
J Biol Chem.
2006 281(37):27134-44.
Bub G, Shrier A, Glass L.
Global
organization of dynamics in oscillatory heterogeneous excitable media.
Phys Rev Lett. 2005 94(2): 028105.
Akhavan A, Atanasiu R, Noguchi T, Han W, Holder N and Shrier|, A
Identification
of the cyclic-nucleotide-binding domain as a conserved determinant of
ion-channel cell-surface localization
Journal of Cell Science 2005 118: 2803-2812
Sherman AJ, Shrier A, Cooper E.
Series resistance compensation for whole-cell patch-clamp studies
using a membrane state estimator.
Biophys J. 1999 Nov;77(5):2590-601.
Petrecca K, Atanasiu R, Grinstein S, Orlowski J, Shrier A.
Subcellular localization of the Na+/H+ exchanger NHE1 in rat
myocardium.
Am J Physiol. 1999 Feb;276(2 Pt 2):H709-17.
Petrecca K, Atanasiu R, Akhavan A, Shrier A.
N-linked glycosylation sites determine HERG channel surface membrane
expression. J Physiol (Lond). 1999 Feb 15;515 ( Pt 1):41-8.
Bub G, Glass L, Publicover NG, Shrier A.
Bursting calcium rotors in cultured cardiac myocyte monolayers.
Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10283-7.
Paquette T, Clay JR, Ogbaghebriel A, Shrier A.
Effects of divalent cations on the E-4031-sensitive repolarization
current, I(Kr), in rabbit ventricular myocytes.
Biophys J. 1998 Mar;74(3):1278-85.
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