Weber 106/107
Phone #: (404) 894-3957, FAX #: (404)894-9982
Research Interests
Research in our laboratory focuses on a class of intracellular ion channels know as ryanodine receptors (RyRs). In mammals, there are three RyR isoforms. RyR1 and RyR2 are the predominate isoforms in skeletal and cardiac muscle, respectively where they are the primary efflux pathway for the release of calcium from the sarcoplasmic reticulum to activate contraction. RyR3 has a wide tissue distribution and contributes to calcium regulation in a variety of cell types. RyRs are the largest known ion channel and are regulated by a multitude of endogenous effectors, including ions, metabolites and regulatory proteins. Therefore, an area of interest is the regulation of these RyR channels by endogenous effectors; especially as it relates to altered contractile function associated with cardiac ischemia/reperfusion, skeletal muscle fatigue and aging. We analyze channel function on multiples levels of organization. Sarcoplasmic reticulum vesicle [3H]ryanodine binding is used to examine large populations of channels. Individual channels are incorporated into artificial lipid bilayers in order to record single channel currents and assess channel kinetics. Calcium release from permeabilized muscle fibers provides a method of examining RyR function in situ. My research has two long-range goals. The first is to understand how intracellular calcium is regulated and how alterations in the regulation effects cell function. The second goal is to understand the RyR regulatory sites that could potentially be exploited for the development of pharmacological compounds to treat disorders of cellular calcium regulation.
Personnel
- Director: Edward Balog, PhD
- Graduate Student: Angela Kampfer
- Graduate Student: Kristyn Flynt, Fall 2009
- Laboratory Technicain: Pryia Patel
- Collaborators:
- Robert Fitts, PhD, Marquette University
- Deb Farrington, PhD, University of Minnesota
- Sankar Nair, PhD, Chemical and Biomolecular Engineering, Georgia Tech
- Bradley Fruen, PhD, University of Minnesota
- Razvan Cornea, PhD, University of Minnesota
- Jenny Yang, PhD, Georgia State University
Current Research Projects
- Ryanodine Receptor Regulation by S-Adenosyl-L-Methionine (SAM)
In this project we use radioligand binding and single channel recording to determine the mechanism by which SAM regulates RyR2. We also perform proteomic analysis of methylation targets within the sarcoplasmic reticulum. - RyR Function in Aging Muscle
We are determining the effects of aging on RyR1 function using [3H]ryanodine binding and single channel recording. In addition we will define age-induced structural modifications of RyR1 using proteomic techniques. - Excitation-Contraction Coupling in Skeletal Muscle Fatigue
A collaborative project with Dr. Robert Fitts (Marquette University) to determine the mechanism by which low-frequency fatigue alters SR Ca2+ release. - Nanopore Devices for Rapid DNA Sequencing
A collaborative project (Dr. Sankar Nair, PI; Chemical and Biomolecular Engineering, Georgia Tech) to develop a rapid, low-cost method to sequence DNA based on DNA-block of ionic current through nanopores. - Structural Determinates of Calmodulin Regulation of RyRs
This collaborative project, with Dr. Jenny Yang (Ga. St.), uses biophysical and biochemical methods to determine the structural requirements for calmodulin regulation of RyR channels.
Research Opportunities
Research opportunities related to most of the projects listed above are available for graduate and undergraduate students. Dr. Balog is an adjunct member of the School of Biology. Undergraduate students are encouraged to take advantage of funding via the President’s Undergraduate Research Awards (Undergraduate Research Opportunities Program).
Funding
- 2008-2011, AHA SDG 0830022N “S-Adenosyl-L-methionine regulation of cardiac ryanodine receptor calcium release channels.
- 2008-2010 Greater Southeast AHA Pre-Doctoral Fellowship 0815101E (to Ms. Kampfer) “Regulation of the cardiac isoform of the ryanodine receptor (RyR2) by s-adenosyl-L-methionine.”
- 2006-2008 NIH AG023902 “SR calcium release channel regulation in aging muscle.”
Recent Publications
- Balog EM, Lockamy EL, Thomas DD, Ferrington DA. Site-Specific Methionine Oxidation Initiates Calmodulin Degradation by the 20S Proteasome. Biochemistry. 48:3005-3016, 2009.
- Kampfer, A. and Balog, EM. S-Adenosyl-L-methionine activates the cardiac ryanodine receptor. Biochem. Biophys. Res. Comm. 371:606-609, 2008.
- Balog, E.M., L.E. Norton, N.R. Nitu, D.D. Thomas, and B.R. Fruen. Role of calmodulin methionine residues in mediating the productive association with cardiac ryanodine receptors. Am. J. Physiol. 290: H794-H799, 2006.
- Balog, E.M., L.E. Norton, R.A. Bloomquist, R.L. Cornea, D.J. Black, C.F. Louis C.F., D.D. Thomas, and B.R. Fruen. Calmodulin oxidation and methionine to glutamine substitutions reveal methionine residues critical for functional interaction with RyR1. J. Biol. Chem. 278:15615-15621, 2003.
- Fruen, B.R., D.J. Black, R.A. Bloomquist, J.M. Bardy, J.D. Johnson, C.F. Louis, and E.M. Balog. Regulation of the RyR1 and RyR2 Ca2+ release channel isoforms by Ca2+-insensitive mutants of calmodulin. Biochem. 42: 2740-2747, 2003.
- Balog, E.M., N.H. Shomer, B.R. Fruen, and C.F. Louis. Divergent effects of the MHS Arg615→Cys mutation on the Ca2+ and Mg2+ dependence of RyR1. Biophys J. 81:2050-2058, 2001.
- Balog, E.M. and R.H. Fitts. Effects of low intracellular pH and elevated extracellular Ca2+ on the charge movement currents of frog skeletal muscle. J. Appl. Physiol. 90: 228-234, 2001.
- Balog, E.M., P.K. Kane, B.R. Fruen, and C.F. Louis. Mechanisms of inorganic phosphate regulation of the skeletal muscle SR Ca2+ release channel. Am. J. Physiol. 278:C601-C611, 2000.