Biomedical Research Education & Training
Faculty Member

Balser, Jeffrey R., M.D., Ph.D.
Vice Chancellor for Health Affairs
Dean of Vanderbilt University School of Medicine
Professor of Anesthesiology
Professor of Pharmacology
Professor of Medicine

Lab Url: https://medschool.vanderbilt.edu/dean/biography

Phone Number: (615) 936-3030

Email Address: jeff.balser@vanderbilt.edu

Balser, Jeffrey's picture
Academic history
B.S.Engr., Tulane University
Ph.D., Vanderbilt University
M.D., Vanderbilt University

Office Address   Mailing Address

D-3300 MC

D-3300 MCN 2104


Research Keywords
biophysics, voltage-gated ion channels, molecula pharmacology, mutagenesis, patch-clamp,

Research Specialty
The biophysics of voltage-gated ion channel channels.

Research Description
Dr. Balser's laboratory examines structure-function relationships in voltage-gated ion channels, with the goal of understanding the molecular action of antiarrhythmic, anticonvulsant, and local anesthetic compounds. Studies have focused primarily on voltage-gated sodium channels, and combine site-directed mutagenesis with patch clamp measurements to discern the influence of gating processes on drug action. Recent studies have focused on amino acid residues in the P-loop, which influence both sodium permeation and a novel slow inactivation gating process that produces structural rearrangements in the outer pore. With the assistance of mathematical models, the laboratory is examining two competing hypotheses: do drugs act primarily by blocking channels (e.g., plugging the pore), or rather by inducing channel conformational changes? Future studies will use fluorescence labels to examine these competing hypotheses directly.

A second, newer focus of the lab is the molecular pharmacology of Class III antiarrhythmic drugs. Studies-to-date have primarily involved HERG, a potassium channel prominent in human atrium and ventricle, and a major target for Class III agents. The HERG channel possesses a unique ultra-rapid inactivation gating mechanism that heavily influences both antiarrhythmic drug action and the exquisite sensitivity of the channel to external potassium. Using cysteine-scanning mutagenesis, patch clamp methods, and mathematical models, the laboratory has examined the complex mechanistic relationships between these biophysical phenomena.

Publications
Nakajima, T, Hayashi, K, Viswanathan, PC, Kim, MY, Anghelescu, M, Barksdale, KA, Shuai, W, Balser, JR, Kupershmidt, S. HERG is protected from pharmacological block by alpha-1,2-glucosyltransferase function. J Biol Chem, 282(8), 5506-13, 2007

Shah, VN, Wingo, TL, Weiss, KL, Williams, CK, Balser, JR, Chazin, WJ. Calcium-dependent regulation of the voltage-gated sodium channel hH1: intrinsic and extrinsic sensors use a common molecular switch. Proc Natl Acad Sci U S A, 103(10), 3592-7, 2006 PMCID:1450128

Viswanathan, PC, Balser, JR. Molecular basis of isolated cardiac conduction disease. Handb Exp Pharmacol(171), 331-47, 2006

Fukuda, K, Davies, SS, Nakajima, T, Ong, BH, Kupershmidt, S, Fessel, J, Amarnath, V, Anderson, ME, Boyden, PA, Viswanathan, PC, Roberts, LJ, Balser, JR. Oxidative mediated lipid peroxidation recapitulates proarrhythmic effects on cardiac sodium channels. Circ Res, 97(12), 1262-9, 2005

Fukuda, Koji, Nakajima, Tadashi, Viswanathan, Prakash C, Balser, Jeffrey R. Compound-specific Na+ channel pore conformational changes induced by local anaesthetics. J Physiol, 564(Pt 1), 21-31, 2005 PMCID:1456037

Mullins, FM, Stepanovic, SZ, Gillani, NB, George, AL, Balser, JR. Functional interaction between extracellular sodium, potassium and inactivation gating in HERG channels. J Physiol, 558(Pt 3), 729-44, 2004 PMCID:1665011

Petersen, CI, McFarland, TR, Stepanovic, SZ, Yang, P, Reiner, DJ, Hayashi, K, George, AL, Roden, DM, Thomas, JH, Balser, JR. In vivo identification of genes that modify ether-a-go-go-related gene activity in Caenorhabditis elegans may also affect human cardiac arrhythmia. Proc Natl Acad Sci U S A, 101(32), 11773-8, 2004 PMCID:511051

Thompson, A, Balser, JR. Perioperative cardiac arrhythmias. Br J Anaesth, 93(1), 86-94, 2004

Viswanathan, PC, Balser, JR. Inherited sodium channelopathies: a continuum of channel dysfunction. Trends Cardiovasc Med, 14(1), 28-35, 2004

Wingo, TL, Shah, VN, Anderson, ME, Lybrand, TP, Chazin, WJ, Balser, JR. An EF-hand in the sodium channel couples intracellular calcium to cardiac excitability. Nat Struct Mol Biol, 11(3), 219-25, 2004

Kupershmidt, S, Yang, IC, Hayashi, K, Wei, J, Chanthaphaychith, S, Petersen, CI, Johns, DC, George, AL, Roden, DM, Balser, JR. The IKr drug response is modulated by KCR1 in transfected cardiac and noncardiac cell lines. FASEB J, 17(15), 2263-5, 2003

Viswanathan, Prakash C, Benson, D Woodrow, Balser, Jeffrey R. A common SCN5A polymorphism modulates the biophysical effects of an SCN5A mutation. J Clin Invest, 111(3), 341-6, 2003 PMCID:151865

Balser, JR. Perioperative arrhythmias: incidence, risk assessment, evaluation, and management. Card Electrophysiol Rev, 6(1-2), 96-9, 2002

Dzhura, I, Wu, Y, Colbran, RJ, Corbin, JD, Balser, JR, Anderson, ME. Cytoskeletal disrupting agents prevent calmodulin kinase, IQ domain and voltage-dependent facilitation of L-type Ca2+ channels. J Physiol, 545(Pt 2), 399-406, 2002 PMCID:2290681

Kupershmidt, S, Yang, IC, Sutherland, M, Wells, KS, Yang, T, Yang, P, Balser, JR, Roden, DM. Cardiac-enriched LIM domain protein fhl2 is required to generate I(Ks) in a heterologous system. Cardiovasc Res, 56(1), 93-103, 2002

Mullins, FM, Stepanovic, SZ, Desai, RR, George, AL, Balser, JR. Extracellular sodium interacts with the HERG channel at an outer pore site. J Gen Physiol, 120(4), 517-37, 2002 PMCID:2229534

Roden, DM, Balser, JR, George, AL, Anderson, ME. Cardiac ion channels. Annu Rev Physiol, 64, 431-75, 2002

Tan, HL, Kupershmidt, S, Zhang, R, Stepanovic, S, Roden, DM, Wilde, AA, Anderson, ME, Balser, JR. A calcium sensor in the sodium channel modulates cardiac excitability. Nature, 415(6870), 442-7, 2002

Wang, DW, Viswanathan, PC, Balser, JR, George, AL, Benson, DW. Clinical, genetic, and biophysical characterization of SCN5A mutations associated with atrioventricular conduction block. Circulation, 105(3), 341-6, 2002

Balser, J R. Inherited sodium channelopathies: novel therapeutic and proarrhythmic molecular mechanisms. Trends Cardiovasc Med, 11(6), 229-37, 2001

Balser, JR. The cardiac sodium channel: gating function and molecular pharmacology. J Mol Cell Cardiol, 33(4), 599-613, 2001

Johnson, JP, Balser, JR, Bennett, PB. A novel extracellular calcium sensing mechanism in voltage-gated potassium ion channels. J Neurosci, 21(12), 4143-53, 2001

Viswanathan, P C, Bezzina, C R, George, A L, Roden, D M, Wilde, A A, Balser, J R. Gating-dependent mechanisms for flecainide action in SCN5A-linked arrhythmia syndromes. Circulation, 104(10), 1200-5, 2001

Numaguchi H, Johnson JP, Jr., Petersen CI and Balser JR. A sensitive mechanism for cation modulation of potassium current. Nat Neurosci 3(5):429-430, 2000.

Chen Z, Ong BH, Kambouris NG, Marban E, Tomaselli GF and Balser JR. Lidocaine induces a slow inactivated state in rat skeletal muscle sodium channels. J Physiol , 524, 137-149, 2000

Chen, Z, Ong, BH, Kambouris, NG, Marb?!n, E, Tomaselli, GF, Balser, JR. Lidocaine induces a slow inactivated state in rat skeletal muscle sodium channels. J Physiol, 524 Pt 1, 37-49, 2000 PMCID:2269847

Dzhura I, Wu Y, Colbran RJ, Balser JR and Anderson ME. Calmodulin kinase determines calcium-dependent facilitation of L-type calcium channels. Nat Cell Biol , 2(3), 173-177, 2000

Dzhura, I, Wu, Y, Colbran, RJ, Balser, JR, Anderson, ME. Calmodulin kinase determines calcium-dependent facilitation of L-type calcium channels. Nat Cell Biol, 2(3), 173-7, 2000

Kambouris NG, Nuss HB, Johns DC, Marban E, Tomaselli GF and Balser JR. A revised view of cardiac sodium channel "blockade" in the long-QT syndrome. J Clin Invest , 105(8), 1133-1140, 2000

Numaguchi, H, Johnson, JP, Petersen, CI, Balser, JR. A sensitive mechanism for cation modulation of potassium current. Nat Neurosci, 3(5), 429-30, 2000

Numaguchi, H, Mullins, FM, Johnson, JP, Johns, DC, Po, SS, Yang, IC, Tomaselli, GF, Balser, JR. Probing the interaction between inactivation gating and Dd-sotalol block of HERG. Circ Res, 87(11), 1012-8, 2000

Nuss HB, Marban E, Tomaselli GF, Balser JR. Isoform-Specific Lidocaine Block of Sodium Channels Rationalized by Differences in Gating. Biophysical Journal, 78, 200-210, 2000

Ong, BH, Tomaselli, GF, Balser, JR. A structural rearrangement in the sodium channel pore linked to slow inactivation and use dependence. J Gen Physiol, 116(5), 653-62, 2000 PMCID:2229478

Wang, DW, Makita, N, Kitabatake, A, Balser, JR, George, AL. Enhanced Na(+) channel intermediate inactivation in Brugada syndrome. Circ Res, 87(8), E37-43, 2000

Balser JR. Sodium ?channelopathies? and sudden death: must you be so sensitive? . Circulation Research, 85, 872-874, 1999

Balser JR. . Structure and function of the cardiac sodium channels. Cardiovascular Research, 42, 327-338, 1999

Balser JR. Structure and function of the cardiac sodium channels. Cardiovasc Res, 42(2), 327-338, 1999

Balser, JR. Structure and function of the cardiac sodium channels. Cardiovasc Res, 42(2), 327-38, 1999

Benitah JP, Chen Z, Balser JR, Tomaselli GF and Marban E. Molecular dynamics of the sodium channel pore vary with gating: Interactions between P-segment motions and inactivation.. J Neurosci, 19(5), 1577-1585, 1999

Benitah JP, Chen Z, Balser JR, Tomaselli GF, Marban E. Molecular dynamics of the sodium channel pore vary with gating: interactions between P-segment motions and inactivation. Journal of Neuroscience, 19, 1577-1585, 1999

Johnson JP, Balser JR, Bennett PB. Enhancement of HERG K currents by destabilization of the inactivated state. Biophysical Journal, 77, 2534-2541, 1999

Johnson, JP, Balser, JR, Bennett, PB. Enhancement of HERG K(+) currents by Cd(2+) destabilization of the inactivated stat. Biophys J, 77(5), 2534-41, 1999

Johnson, JP, Balser, JR, Bennett, PB. Enhancement of HERG K(+) currents by Cd(2+) destabilization of the inactivated stat. Biophys J, 77(5), 2534-41, 1999 PMCID:1300528

Balser JR, Martinez EA,Winters BD, Purdue PW, Clarke AW, Huang W, Tomaselli GF, Dorman T, Campbell K, Lipsett P, Breslow MJ, Rosenfeld BA. -adrenergic blockade accelerates conversion of postoperative supraventricular tachycardia. Anesthesiology, 89, 1052-1059, 1998

Balser, JR. The molecular pharmacology of local anesthetic/antiarrhythmic agents. Trends in Cardiovascular Medicine, 8, 83-88, 1998

Dorman T, Breslow MJ, Lipsett PA, Rosenberg JM, Balser JR, Almog Y, Rosenfeld BA. Radial artery pressure monitoring underestimates central arterial pressure during vasopressor therapy in critically ill surgical patients. Critical Care Medicine , 10, 1646-1649, 1998

Kambouris N, Hastings L, Stepanovic S, Marban E, Tomaselli GF, Balser JR. Mechanistic link between local anaesthetic action and inactivation gating probed by outer pore mutations in the rat 1 sodium channel. Journal of Physiology, 512, 693-705, 1998

Kambouris NG, Nuss HB, Johns DC, Tomaselli GF, Marban E, Balser JR. Phenotypic characterization of a novel long QT syndrome mutation in the cardiac sodium channel. Circulation, 97, 640-644, 1998

Perdue PW, Balser JR, Lipsett PA, Breslow MJ. "Renal-dose? dopamine in surgical patients: Dogma or science?. Annals of Surgery, 227, 470-473, 1998

Pu, J, Balser JR, Boyden PA. Lidocaine action on sodium currents in ventricular myocytes from the epicardial border zone of the infarcted heart. Circulation Research , 83, 431-440, 1998

Balser JR. The rational use of intravenous amiodarone in the perioperative period. Anesthesiology, 86, 974-987, 1997

Benitah JP, Balser JR, Marban E, Tomaselli GF. Proton Inhibition of sodium channels: mechanism of gating shifts and reduced conductance. Journal of Membrane Biology , 155, 121-131, 1997

Perez-Garcia MT, Chiamvimonvat N, Ranjan R, Balser JR, Tomaselli GF, Marban E. Mechanisms of sodium/calcium selectivity in sodium channels probed by cysteine mutagenesis and sulfhydryl modification. Biophysical Journal, 72, 989-996, 1997

Schultheis LW, Balser JR, Calkins H, Robertson S, Weiss JL, Sussman M, Stuart RS. High dose neostigmine treatment of sinus tachycardia. PACE, 20, 1369-1373, 1997

Balser JR, Nuss HB, Romashko, DN, Marban E, Tomaselli, GF. Functional consequences of lidocaine binding to slow-inactivated sodium channels. Journal of General Physiology , 107, 6438-658, 1996

Balser JR, Nuss HB, Chiamvimonvat N, Perez-Garcia MT, Marban E, Tomaselli GF. External pore residue mediates slow inactivation in 1 rat skeletal muscle sodium channels. Journal of Physiology , 494, 431-442, 1996

Balser JR, Nuss HB, Orias DW, Johns DC, Marban E, Tomaselli GF, Lawrence JH. Local anesthetics as effectors of allosteric gating: lidocaine effects on inactivation-deficient rat skeletal muscle Na channels. Journal of Clinical Investigation , 98, 2874-2886, 1996

Lawrence, JH, Orias DW, Balser JR, Nuss HB, Tomaselli, GF, Marban E. Single-channel analysis of inactivation-defective rat skeletal muscle sodium channels containing the F1304Q mutation. Biophysical Journal , 71, 1285-1294, 1996

Nuss HB, Balser JR, Orias DW, Lawrence JH, Tomaselli GF, Marban E. Coupling between fast and slow inactivation revealed by analysis of a point mutation (F1304Q) in 1 rat skeletal muscle sodium channels. Journal of Physiology , 494, 411-429, 1996

Tomaselli GF, Chiamvimonvat N, Nuss HB, Balser JR, Perez-Garcia, MT, Kluge K, Orias DW, Backx PH, Marban E. A Mutation in the pore of the sodium channel that alters gating. Biophysical Journal , 68, 1814-1827, 1995

Balser JR, Bennett PB, Hondeghem LM, Roden DM. Suppression of time-dependent outward current in guinea pig ventricular myocytes: actions of quinidine and amiodarone. Circulation Research , 69, 519-529, 1991

Balser, JR, Bennett, PB, Hondeghem, LM, Roden, DM. Suppression of time-dependent outward current in guinea pig ventricular myocytes. Actions of quinidine and amiodarone. Circ Res, 69(2), 519-29, 1991

Balser, JR, Roden, DM, Bennett, PB. Single inward rectifier potassium channels in guinea pig ventricular myocytes. Effects of quinidine. Biophys J, 59(1), 150-61, 1991 PMCID:1281127

Wikswo JP, Wisialowski TA, Altemeier WA, Balser JR, Kopelman HA, Roden DM. Virtual cathode effects during stimulation of cardiac muscle: two-dimensional in vivo experiments. Circulation Research , 68, 513-530, 1991

Wikswo, J P, Wisialowski, T A, Altemeier, W A, Balser, J R, Kopelman, H A, Roden, D M. Virtual cathode effects during stimulation of cardiac muscle. Two-dimensional in vivo experiments. Circ Res, 68(2), 513-30, 1991

Balser JR, Bennett PB, Roden DM. Time-dependent outward current in guinea pig ventricular myocytes: gating kinetics of the delayed rectifier. Journal of General Physiology , 96, 835-863, 1990

Balser JR, Roden DM, and Bennett PB. Global parameter optimization for cardiac potassium channel gating models. Biophysical Journal , 57, 433-444, 1990

Balser JR, Roden DM, and Bennett PB. Single inward rectifier potassium channels in guinea pig ventricular myocytes: effects of quinidine. Biophysical Journal, 59, 150-161, 1990

Balser, J R, Roden, D M, Bennett, P B. Global parameter optimization for cardiac potassium channel gating models. Biophys J, 57(3), 433-44, 1990 PMCID:1280738

Balser, JR, Bennett, PB, Roden, DM. Time-dependent outward current in guinea pig ventricular myocytes. Gating kinetics of the delayed rectifier. J Gen Physiol, 96(4), 835-63, 1990 PMCID:2229010

Roden DM, Bennett PB, Snyders DJ, Balser JR, and Hondeghem LM. Quinidine delays IK activation in guinea pig ventricular myocytes. Circulation Research , 62, 1055-1058, 1988

Roden, DM, Bennett, PB, Snyders, DJ, Balser, JR, Hondeghem, LM. Quinidine delays IK activation in guinea pig ventricular myocytes. Circ Res, 62(5), 1055-8, 1988

Cowin SC, Hart RT, Balser JR, Kohn DH. Functional adaptation in long bones: establishing in vivo values for surface remodeling rate coefficients. Journal of Biomechanics, 18(9), 665-684, 1985


Postdoctoral Position Available
No

Postdoctoral Position Details
N/A

Updated Date
12/09/2009