Vanderbilt University School of
1265 Medical Research Building IV
1265 MRBIV 37232-0575
My laboratory is interested in the biology of cardiac arrhythmias. Using genetically-altered mice as model systems, ongoing research examines several key pathways of arrhythmias and sudden death in humans:
1) Impaired cardiac calcium cycling and mutations in cardiac Ca2+ handling proteins, 2) Troponin T mutations associated with hypertrophic cardiomyopathy and 3) Mutations associated with the congenital long QT syndrome. In neither case the mechanisms that lead to sudden cardiac death are fully understood.
The laboratory performs comprehensive studies from the molecular level to the whole animal in each mouse model in order to better understand the mechanisms of arrhythmogenesis. For example, single cell patch-clamp, intracellular calcium and cell shortening measurements, whole-heart electro-physiology and contractility measurements, and in vivo electrocardiogram and hemodynamic studies are performed. This research may identify therapeutic strategies, which then can be tested in the same model system prior to human studies.
Faggioni, M, Hwang, HS, van der Werf, C, Nederend, I, Kannankeril, PJ, Wilde, AA, Knollmann, BC. Accelerated sinus rhythm prevents catecholaminergic polymorphic ventricular tachycardia in mice and in patients. Circ Res, 112(4), 689-97, 2013.
Huke, S, Venkataraman, R, Faggioni, M, Bennuri, S, Hwang, HS, Baudenbacher, F, Knollmann, BC. Focal energy deprivation underlies arrhythmia susceptibility in mice with calcium-sensitized myofilaments. Circ Res, 112(10), 1334-44, 2013.
Knollmann, BC. Induced pluripotent stem cell-derived cardiomyocytes: boutique science or valuable arrhythmia model. Circ Res, 112(6), 969-76; discussion 976, 2013.
Roderick, HL, Knollmann, BC. Inositol 1,4,5-trisphosphate receptors: "exciting" players in cardiac excitation-contraction coupling. Circulation, 128(12), 1273-5, 2013.
Venkataraman, R, Baldo, MP, Hwang, HS, Veltri, T, Pinto, JR, Baudenbacher, FJ, Knollmann, BC. Myofilament calcium de-sensitization and contractile uncoupling prevent pause-triggered ventricular tachycardia in mouse hearts with chronic myocardial infarction. J Mol Cell Cardiol, 60, 8-15, 2013.
Faggioni, M, Knollmann, BC. Calsequestrin 2 and arrhythmias. Am J Physiol Heart Circ Physiol, 302(6), H1250-60, 2012.
Faggioni, M, Kryshtal, DO, Knollmann, BC. Calsequestrin mutations and catecholaminergic polymorphic ventricular tachycardia. Pediatr Cardiol, 33(6), 959-67, 2012.
Schober, T, Huke, S, Venkataraman, R, Gryshchenko, O, Kryshtal, D, Hwang, HS, Baudenbacher, FJ, Knollmann, BC. Myofilament Ca sensitization increases cytosolic Ca binding affinity, alters intracellular Ca homeostasis, and causes pause-dependent Ca-triggered arrhythmia. Circ Res, 111(2), 170-9, 2012.
Venkataraman, R, Holcomb, MR, Harder, R, Knollmann, BC, Baudenbacher, F. Ratiometric imaging of calcium during ischemia-reperfusion injury in isolated mouse hearts using Fura-2. Biomed Eng Online, 11, 39, 2012.
Chopra, N, Knollmann, BC. Genetics of sudden cardiac death syndromes. Curr Opin Cardiol, 26(3), 196-203, 2011.
Galimberti, ES, Knollmann, BC. Efficacy and potency of class I antiarrhythmic drugs for suppression of Ca2+ waves in permeabilized myocytes lacking calsequestrin. J Mol Cell Cardiol, 51(5), 760-8, 2011.
Hwang, HS, Hasdemir, C, Laver, D, Mehra, D, Turhan, K, Faggioni, M, Yin, H, Knollmann, BC. Inhibition of cardiac Ca2+ release channels (RyR2) determines efficacy of class I antiarrhythmic drugs in catecholaminergic polymorphic ventricular tachycardia. Circ Arrhythm Electrophysiol, 4(2), 128-35, 2011.
Watanabe, H, Yang, T, Stroud, DM, Lowe, JS, Harris, L, Atack, TC, Wang, DW, Hipkens, SB, Leake, B, Hall, L, Kupershmidt, S, Chopra, N, Magnuson, MA, Tanabe, N, Knollmann, BC, George, AL, Roden, DM. Striking In vivo phenotype of a disease-associated human SCN5A mutation producing minimal changes in vitro. Circulation, 124(9), 1001-11, 2011.
Hilliard, FA, Steele, DS, Laver, D, Yang, Z, Le Marchand, SJ, Chopra, N, Piston, DW, Huke, S, Knollmann, BC. Flecainide inhibits arrhythmogenic Ca2+ waves by open state block of ryanodine receptor Ca2+ release channels and reduction of Ca2+ spark mass. J Mol Cell Cardiol, 48(2), 293-301, 2010.
Huke, S, Knollmann, BC. Increased myofilament Ca2+-sensitivity and arrhythmia susceptibility. J Mol Cell Cardiol, 48(5), 824-33, 2010.
Knollmann, BC. Pacing lightly: optogenetics gets to the heart. Nat Methods, 7(11), 889-91, 2010.
Chopra, N, Knollmann, BC. Cardiac Calsequestrin: The New Kid on the Block in Arrhythmias. J Cardiovasc Electrophysiol, , , 2009.
Chopra, N, Laver, D, Davies, SS, Knollmann, BC. Amitriptyline activates cardiac ryanodine channels and causes spontaneous sarcoplasmic reticulum calcium release. Mol Pharmacol, 75(1), 183-95, 2009. PMCID:2685059
Chopra, N, Yang, T, Asghari, P, Moore, ED, Huke, S, Akin, B, Cattolica, RA, Perez, CF, Hlaing, T, Knollmann-Ritschel, BE, Jones, LR, Pessah, IN, Allen, PD, Franzini-Armstrong, C, Knollmann, BC. Ablation of triadin causes loss of cardiac Ca2+ release units, impaired excitation-contraction coupling, and cardiac arrhythmias. Proc Natl Acad Sci U S A, 106(18), 7636-41, 2009. PMCID:2678594
Knollmann, BC. New roles of calsequestrin and triadin in cardiac muscle. J Physiol, 587(Pt 13), 3081-7, 2009. PMCID:2727016
Watanabe, H, Chopra, N, Laver, D, Hwang, HS, Davies, SS, Roach, DE, Duff, HJ, Roden, DM, Wilde, AA, Knollmann, BC. Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans. Nat Med, 15(4), 380-3, 2009.
Baudenbacher, F, Schober, T, Pinto, JR, Sidorov, VY, Hilliard, F, Solaro, RJ, Potter, JD, Knollmann, BC. Myofilament Ca2+ sensitization causes susceptibility to cardiac arrhythmia in mice. J Clin Invest, 118(12), 3893-903, 2008.
Knollmann, BC, Roden, DM. A genetic framework for improving arrhythmia therapy. Nature, 451(7181), 929-36, 2008.
Raj, SR, Knollmann, BC. The beat goes on--driven by a cardiac calcium clock. Heart Rhythm, 5(5), 701-3, 2008. PMCID:2577818
Chopra, N, Kannankeril, PJ, Yang, T, Hlaing, T, Holinstat, I, Ettensohn, K, Pfeifer, K, Akin, B, Jones, LR, Franzini-Armstrong, C, Knollmann, BC. Modest reductions of cardiac calsequestrin increase sarcoplasmic reticulum Ca2+ leak independent of luminal Ca2+ and trigger ventricular arrhythmias in mice. Circ Res, 101(6), 617-26, 2007.
Knollmann, BC, Schober, T, Petersen, AO, Sirenko, SG, Franz, MR. Action potential characterization in intact mouse heart: steady-state cycle length dependence and electrical restitution. Am J Physiol Heart Circ Physiol, 292(1), H614-21, 2007.
Knollmann, BC, Sirenko, S, Rong, Q, Katchman, AN, Casimiro, M, Pfeifer, K, Ebert, SN. Kcnq1 contributes to an adrenergic-sensitive steady-state K+ current in mouse heart. Biochem Biophys Res Commun, 360(1), 212-8, 2007. PMCID:2025686
Schober, T, Knollmann, BC. Exercise after myocardial infarction improves contractility and decreases myofilament Ca2+ sensitivity. Circ Res, 100(7), 937-9, 2007.
Knollmann, BC, Chopra, N, Hlaing, T, Akin, B, Yang, T, Ettensohn, K, Knollmann, BE, Horton, KD, Weissman, NJ, Holinstat, I, Zhang, W, Roden, DM, Jones, LR, Franzini-Armstrong, C, Pfeifer, K. Casq2 deletion causes sarcoplasmic reticulum volume increase, premature Ca2+ release, and catecholaminergic polymorphic ventricular tachycardia. J Clin Invest, 116(9), 2510-20, 2006. PMCID:1551934
Sirenko, SG, Potter, JD, Knollmann, BC. Differential effect of troponin T mutations on the inotropic responsiveness of mouse hearts--role of myofilament Ca2+ sensitivity increase. J Physiol, 575(Pt 1), 201-13, 2006. PMCID:1819413
Hernandez, OM, Szczesna-Cordary, D, Knollmann, BC, Miller, T, Bell, M, Zhao, J, Sirenko, SG, Diaz, Z, Guzman, G, Xu, Y, Wang, Y, Kerrick, WG, Potter, JD. F110I and R278C troponin T mutations that cause familial hypertrophic cardiomyopathy
affect muscle contraction in transgenic mice and reconstituted human cardiac fibers. J Biol Chem, 280(44), 37183-94, 2005.
Knollmann, BC, Smyth, BJ, Garnett, CE, Salesiotis, AN, Gvozdjan, DM, Berry, NS, Lee, H, Min, FD. Personal digital assistant-based drug reference software as tools to improve
rational prescribing: benchmark criteria and performance. Clin Pharmacol Ther, 78(1), 7-18, 2005.
Morad, M, Cleemann, L, Knollmann, BC. Triadin: the new player on excitation-contraction coupling block. Circ Res, 96(6), 607-9, 2005.
Westermann, D, Knollmann, BC, Steendijk, P, Rutschow, S, Riad, A, Pauschinger, M, Potter, JD, Schultheiss, HP, Tschope, C. Diltiazem treatment prevents diastolic heart failure in mice with familial
hypertrophic cardiomyopathy. Eur J Heart Fail, 8(2), 115-121, 2005.
Casimiro, MC, Knollmann, BC, Yamoah, EN, Nie, L, Vary, JC, Sirenko, SG, Greene, AE, Grinberg, A, Huang, SP, Ebert, SN, Pfeifer, K. Targeted point mutagenesis of mouse Kcnq1: phenotypic analysis of mice with
point mutations that cause Romano-Ward syndrome in humans. Genomics, 84(3), 555-64, 2004.
Knollmann, BC, Casimiro, MC, Katchman, AN, Sirenko, SG, Schober, T, Rong, Q, Pfeifer, K, Ebert, SN. Isoproterenol exacerbates a long QT phenotype in Kcnq1-deficient neonatal mice:
possible roles for human-like Kcnq1 isoform 1 and slow delayed rectifier K+ current. J Pharmacol Exp Ther, 310(1), 311-8, 2004.
Tranquillo, JV, Franz, MR, Knollmann, BC, Henriquez, AP, Taylor, DA, Henriquez, CS. Genesis of the monophasic action potential: role of interstitial resistance
and boundary gradients. Am J Physiol Heart Circ Physiol, 286(4), H1370-81, 2004.
Knollmann, BC, Kirchhof, P, Sirenko, SG, Degen, H, Greene, AE, Schober, T, Mackow, JC, Fabritz, L, Potter, JD, Morad, M. Familial hypertrophic cardiomyopathy-linked mutant troponin T causes stress-induced
ventricular tachycardia and Ca2+-dependent action potential remodeling. Circ Res, 92(4), 428-36, 2003.
Flockhart, DA, Usdin Yasuda, S, Pezzullo, JC, Knollmann, BC. Teaching rational prescribing: a new clinical pharmacology curriculum for medical
schools. Naunyn Schmiedebergs Arch Pharmacol, 366(1), 33-43, 2002.
Ji, S, Tosaka, T, Whitfield, BH, Katchman, AN, Kandil, A, Knollmann, BC, Ebert, SN. Differential rate responses to nicotine in rat heart: evidence for two classes
of nicotinic receptors. J Pharmacol Exp Ther, 301(3), 893-9, 2002.
Knollmann, BC, Tranquillo, J, Sirenko, SG, Henriquez, C, Franz, MR. Microelectrode study of the genesis of the monophasic action potential by contact
electrode technique. J Cardiovasc Electrophysiol, 13(12), 1246-52, 2002.
Casimiro, MC, Knollmann, BC, Ebert, SN, Vary, JC, Greene, AE, Franz, MR, Grinberg, A, Huang, SP, Pfeifer, K. Targeted disruption of the Kcnq1 gene produces a mouse model of Jervell and
Lange-Nielsen Syndrome. Proc Natl Acad Sci U S A, 98(5), 2526-31, 2001. PMCID:30171
Knollmann, BC, Blatt, SA, Horton, K, de Freitas, F, Miller, T, Bell, M, Housmans, PR, Weissman, NJ, Morad, M, Potter, JD. Inotropic stimulation induces cardiac dysfunction in transgenic mice expressing
a troponin T (I79N) mutation linked to familial hypertrophic cardiomyopathy. J Biol Chem, 276(13), 10039-48, 2001.
Knollmann, BC, Katchman, AN, Franz, MR. Monophasic action potential recordings from intact mouse heart: validation,
regional heterogeneity, and relation to refractoriness. J Cardiovasc Electrophysiol, 12(11), 1286-94, 2001.
Knollmann, BC, Potter, JD. Altered regulation of cardiac muscle contraction by troponin T mutations that
cause familial hypertrophic cardiomyopathy. Trends Cardiovasc Med, 11(5), 206-12, 2001.
Knollmann, BC, Knollmann-Ritschel, BE, Weissman, NJ, Jones, LR, Morad, M. Remodelling of ionic currents in hypertrophied and failing hearts of transgenic
mice overexpressing calsequestrin. J Physiol, 525 Pt 2, 483-98, 2000. PMCID:2269956
Knollman, BC. Electrical remodeling and cardiac phenotype of transgenic mice overexpressing calsequestrin. Ph.D. Dissertation, Georgetown University, , 1999.
Behrens, S, Li, C, Knollmann, BC, Franz, MR. Dispersion of ventricular repolarization in the voltage domain. Pacing Clin Electrophysiol, 21(1 Pt 1), 100-7, 1998.
Drici, MD, Knollmann, BC, Wang, WX, Woosley, RL. Cardiac actions of erythromycin: influence of female sex. JAMA, 280(20), 1774-6, 1998.
Knollmann, BC, Corson, AP, Twigg, HL, Schulman, KA. Assessment of joint review of radiologic studies by a primary care physician
and a radiologist. J Gen Intern Med, 11(10), 608-12, 1996.
Experience in patch-clamping and intracellular calcium measurments of cardiac myocytes beneficial
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