Bjorn C. Knollmann, M.D., Ph.D.

Professor

bjorn.knollmann@vanderbilt.edu

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Faculty Appointments
Professor of Medicine Professor of Pharmacology
Education
Ph.D., Pharmacology, Georgetown University, Washington, District of ColumbiaM.D., Medicine, University of Cincinnati, Cincinnati, Ohio
Office Address
1265 MRBIV
2215B Garland Avenue, Room 1265
Nashville, TN 37232-0575
Research Description
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.
Publications
Roderick HL, Knollmann BC. Inositol 1,4,5-trisphosphate receptors: "exciting" players in cardiac excitation-contraction coupling? [editorial]. Circulation [print-electronic]. 2013 Sep 9/17/2013; 128(12): 1273-5. PMID: 23983251, PMCID: PMC3885819, PII: CIRCULATIONAHA.113.005157, DOI: 10.1161/CIRCULATIONAHA.113.005157, ISSN: 1524-4539.

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 [print-electronic]. 2013 Jul; 60: 8-15. PMID: 23570978, PMCID: PMC3683590, PII: S0022-2828(13)00103-X, DOI: 10.1016/j.yjmcc.2013.03.022, ISSN: 1095-8584.

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 [print-electronic]. 2013 May 5/10/2013; 112(10): 1334-44. PMID: 23532597, PMCID: PMC3850761, PII: CIRCRESAHA.113.301055, DOI: 10.1161/CIRCRESAHA.113.301055, ISSN: 1524-4571.

Knollmann BC. Induced pluripotent stem cell-derived cardiomyocytes: boutique science or valuable arrhythmia model?. Circ. Res. 2013 Mar 3/15/2013; 112(6): 969-76; discussion 976. PMID: 23569106, PMCID: PMC3667201, PII: 112/6/969, DOI: 10.1161/CIRCRESAHA.112.300567, ISSN: 1524-4571.

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 [print-electronic]. 2013 Feb 2/15/2013; 112(4): 689-97. PMID: 23295832, PMCID: PMC3601570, PII: CIRCRESAHA.111.300076, DOI: 10.1161/CIRCRESAHA.111.300076, ISSN: 1524-4571.

Faggioni M, Kryshtal DO, Knollmann BC. Calsequestrin mutations and catecholaminergic polymorphic ventricular tachycardia. Pediatr Cardiol [print-electronic]. 2012 Aug; 33(6): 959-67. PMID: 22421959, PMCID: PMC3393815, DOI: 10.1007/s00246-012-0256-1, ISSN: 1432-1971.

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 [print-electronic]. 2012 Jul 7/6/2012; 111(2): 170-9. PMID: 22647877, PMCID: PMC3393041, PII: CIRCRESAHA.112.270041, DOI: 10.1161/CIRCRESAHA.112.270041, ISSN: 1524-4571.

Faggioni M, Knollmann BC. Calsequestrin 2 and arrhythmias. Am. J. Physiol. Heart Circ. Physiol [print-electronic]. 2012 Mar 3/15/2012; 302(6): H1250-60. PMID: 22198169, PMCID: PMC3311477, PII: ajpheart.00779.2011, DOI: 10.1152/ajpheart.00779.2011, ISSN: 1522-1539.

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. 2012; 11: 39. PMID: 22812644, PMCID: PMC3466138, PII: 1475-925X-11-39, DOI: 10.1186/1475-925X-11-39, ISSN: 1475-925X.

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 [print-electronic]. 2011 Nov; 51(5): 760-8. PMID: 21798265, PMCID: PMC3184367, PII: S0022-2828(11)00266-5, DOI: 10.1016/j.yjmcc.2011.07.002, ISSN: 1095-8584.

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 [print-electronic]. 2011 Aug 8/30/2011; 124(9): 1001-11. PMID: 21824921, PMCID: PMC3297976, PII: CIRCULATIONAHA.110.987248, DOI: 10.1161/CIRCULATIONAHA.110.987248, ISSN: 1524-4539.

Chopra N, Knollmann BC. Genetics of sudden cardiac death syndromes. Curr. Opin. Cardiol. 2011 May; 26(3): 196-203. PMID: 21430528, PMCID: PMC3145336, DOI: 10.1097/HCO.0b013e3283459893, ISSN: 1531-7080.

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 [print-electronic]. 2011 Apr; 4(2): 128-35. PMID: 21270101, PMCID: PMC3667204, PII: CIRCEP.110.959916, DOI: 10.1161/CIRCEP.110.959916, ISSN: 1941-3084.

Knollmann BC. Pacing lightly: optogenetics gets to the heart. Nat. Methods. 2010 Nov; 7(11): 889-91. PMID: 21030965, PII: nmeth1110-889, DOI: 10.1038/nmeth1110-889, ISSN: 1548-7105.

Huke S, Knollmann BC. Increased myofilament Ca2+-sensitivity and arrhythmia susceptibility. J. Mol. Cell. Cardiol [print-electronic]. 2010 May; 48(5): 824-33. PMID: 20097204, PMCID: PMC2854218, PII: S0022-2828(10)00012-X, DOI: 10.1016/j.yjmcc.2010.01.011, ISSN: 1095-8584.

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 [print-electronic]. 2010 Feb; 48(2): 293-301. PMID: 19835880, PMCID: PMC2813417, PII: S0022-2828(09)00428-3, DOI: 10.1016/j.yjmcc.2009.10.005, ISSN: 1095-8584.

Chopra N, Knollmann BC. Cardiac calsequestrin: the new kid on the block in arrhythmias. J. Cardiovasc. Electrophysiol [print-electronic]. 2009 Oct; 20(10): 1179-85. PMID: 19563351, PII: JCE1531, DOI: 10.1111/j.1540-8167.2009.01531.x, ISSN: 1540-8167.

Knollmann BC. New roles of calsequestrin and triadin in cardiac muscle. J. Physiol. (Lond.) [print-electronic]. 2009 Jul 7/1/2009; 587(Pt 13): 3081-7. PMID: 19451205, PMCID: PMC2727016, PII: jphysiol.2009.172098, DOI: 10.1113/jphysiol.2009.172098, ISSN: 1469-7793.

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 [print-electronic]. 2009 May 5/5/2009; 106(18): 7636-41. PMID: 19383796, PMCID: PMC2678594, PII: 0902919106, DOI: 10.1073/pnas.0902919106, ISSN: 1091-6490.

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 [print-electronic]. 2009 Apr; 15(4): 380-3. PMID: 19330009, PMCID: PMC2904954, PII: nm.1942, DOI: 10.1038/nm.1942, ISSN: 1546-170X.

Chopra N, Laver D, Davies SS, Knollmann BC. Amitriptyline activates cardiac ryanodine channels and causes spontaneous sarcoplasmic reticulum calcium release. Mol. Pharmacol [print-electronic]. 2009 Jan; 75(1): 183-95. PMID: 18845675, PMCID: PMC2685059, PII: mol.108.051490, DOI: 10.1124/mol.108.051490, ISSN: 1521-0111.

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 [print-electronic]. 2008 Dec; 118(12): 3893-903. PMID: 19033660, PMCID: PMC2582931, PII: 36642, DOI: 10.1172/JCI36642, ISSN: 0021-9738.

Raj SR, Knollmann BC. The beat goes on--driven by a cardiac calcium clock? [editorial]. Heart Rhythm [print-electronic]. 2008 May; 5(5): 701-3. PMID: 18452872, PMCID: PMC2577818, PII: S1547-5271(08)00208-7, DOI: 10.1016/j.hrthm.2008.02.027, ISSN: 1556-3871.

Knollmann BC, Roden DM. A genetic framework for improving arrhythmia therapy. Nature. 2008 Feb 2/21/2008; 451(7181): 929-36. PMID: 18288182, PII: nature06799, DOI: 10.1038/nature06799, ISSN: 1476-4687.

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 [print-electronic]. 2007 Sep 9/14/2007; 101(6): 617-26. PMID: 17656677, PII: CIRCRESAHA.107.157552, DOI: 10.1161/CIRCRESAHA.107.157552, ISSN: 1524-4571.

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 [print-electronic]. 2007 Aug 8/17/2007; 360(1): 212-8. PMID: 17597584, PMCID: PMC2025686, PII: S0006-291X(07)01272-7, DOI: 10.1016/j.bbrc.2007.06.038, ISSN: 0006-291X.

Schober T, Knollmann BC. Exercise after myocardial infarction improves contractility and decreases myofilament Ca2+ sensitivity [editorial]. Circ. Res. 2007 Apr 4/13/2007; 100(7): 937-9. PMID: 17431194, PII: 100/7/937, DOI: 10.1161/01.RES.0000265138.06052.08, ISSN: 1524-4571.

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 [print-electronic]. 2007 Jan; 292(1): H614-21. PMID: 16963611, PII: 01085.2005, DOI: 10.1152/ajpheart.01085.2005, ISSN: 0363-6135.

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 [print-electronic]. 2006 Sep; 116(9): 2510-20. PMID: 16932808, PMCID: PMC1551934, DOI: 10.1172/JCI29128, ISSN: 0021-9738.

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. (Lond.) [print-electronic]. 2006 Aug 8/15/2006; 575(Pt 1): 201-13. PMID: 16777946, PMCID: PMC1819413, PII: jphysiol.2006.107557, DOI: 10.1113/jphysiol.2006.107557, ISSN: 0022-3751.

Westermann D, Knollmann BC, Steendijk P, Rutschow S, Riad A, Pauschinger M, Potter JD, Schultheiss HP, Tschöpe C. Diltiazem treatment prevents diastolic heart failure in mice with familial hypertrophic cardiomyopathy. Eur. J. Heart Fail [print-electronic]. 2006 Mar; 8(2): 115-21. PMID: 16214409, PII: S1388-9842(05)00213-8, DOI: 10.1016/j.ejheart.2005.07.012, ISSN: 1388-9842.

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 [print-electronic]. 2005 Nov 11/4/2005; 280(44): 37183-94. PMID: 16115869, PII: M508114200, DOI: 10.1074/jbc.M508114200, ISSN: 0021-9258.

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. 2005 Jul; 78(1): 7-18. PMID: 16003287, PII: S0009923605001360, DOI: 10.1016/j.clpt.2005.03.007, ISSN: 0009-9236.

Morad M, Cleemann L, Knollmann BC. Triadin: the new player on excitation-contraction coupling block [editorial]. Circ. Res. 2005 Apr 4/1/2005; 96(6): 607-9. PMID: 15802617, PII: 96/6/607, DOI: 10.1161/01.RES.0000162162.97722.38, ISSN: 1524-4571.

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. 2004 Sep; 84(3): 555-64. PMID: 15498462, PII: S0888-7543(04)00163-6, DOI: 10.1016/j.ygeno.2004.06.007, ISSN: 0888-7543.

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 [print-electronic]. 2004 Jul; 310(1): 311-8. PMID: 15004216, PII: jpet.103.063743, DOI: 10.1124/jpet.103.063743, ISSN: 0022-3565.

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 [print-electronic]. 2004 Apr; 286(4): H1370-81. PMID: 14656706, PII: 00803.2003, DOI: 10.1152/ajpheart.00803.2003, ISSN: 0363-6135.

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 [print-electronic]. 2003 Mar 3/7/2003; 92(4): 428-36. PMID: 12600890, PII: 01.RES.0000059562.91384.1A, DOI: 10.1161/01.RES.0000059562.91384.1A, ISSN: 1524-4571.

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. 2002 Dec; 13(12): 1246-52. PMID: 12521341, ISSN: 1045-3873.

Flockhart DA, Usdin Yasuda S, Pezzullo JC, Knollmann BC. Teaching rational prescribing: a new clinical pharmacology curriculum for medical schools. Naunyn Schmiedebergs Arch. Pharmacol [print-electronic]. 2002 Jul; 366(1): 33-43. PMID: 12107631, DOI: 10.1007/s00210-002-0559-5, ISSN: 0028-1298.

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. 2002 Jun; 301(3): 893-9. PMID: 12023516, ISSN: 0022-3565.

Knollmann BC, Katchman AN, Franz MR. Monophasic action potential recordings from intact mouse heart: validation, regional heterogeneity, and relation to refractoriness. J. Cardiovasc. Electrophysiol. 2001 Nov; 12(11): 1286-94. PMID: 11761418, ISSN: 1045-3873.

Knollmann BC, Potter JD. Altered regulation of cardiac muscle contraction by troponin T mutations that cause familial hypertrophic cardiomyopathy. Trends Cardiovasc. Med. 2001 Jul; 11(5): 206-12. PMID: 11597833, PII: S1050-1738(01)00115-3, ISSN: 1050-1738.

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 [print-electronic]. 2001 Mar 3/30/2001; 276(13): 10039-48. PMID: 11113119, PII: M006745200, DOI: 10.1074/jbc.M006745200, ISSN: 0021-9258.

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. 2001 Feb 2/27/2001; 98(5): 2526-31. PMID: 11226272, PMCID: PMC30171, PII: 98/5/2526, DOI: 10.1073/pnas.041398998, ISSN: 0027-8424.

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. (Lond.). 2000 Jun 6/1/2000; 525 Pt 2: 483-98. PMID: 10835049, PMCID: PMC2269956, PII: PHY_0541, ISSN: 0022-3751.

Knollman, BC. Electrical remodeling and cardiac phenotype of transgenic mice overexpressing calsequestrin. Ph.D. Dissertation. 1999; Georgetown University.

Drici MD, Knollmann BC, Wang WX, Woosley RL. Cardiac actions of erythromycin: influence of female sex. JAMA. 1998 Nov 11/25/1998; 280(20): 1774-6. PMID: 9842954, PII: jbr80358, ISSN: 0098-7484.

Behrens S, Li C, Knollmann BC, Franz MR. Dispersion of ventricular repolarization in the voltage domain. Pacing Clin Electrophysiol. 1998 Jan; 21(1 Pt 1): 100-7. PMID: 9474654, ISSN: 0147-8389.

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. 1996 Oct; 11(10): 608-12. PMID: 8945692, ISSN: 0884-8734.

Berliner, M, Knollmann, BC, Schmidt, KL. Effects of different methods of cryotherapy on skin microcirculation and skin temperature of the wrist (in German). Physikalische Medizin Rehabilitationsmedizin, Kurortmedizin. 1995; 5: 46-51.

Knollmann, BC. Wirkungen unterschiedlicher Kryotherapieverfahren auf Hautdurchblutung und Hauttemperatur am Handgelenk. Medical Dissertation (Dr. Med.) Justus-Liebig-University Giessen. 1995.

Available Postdoctoral Position Details
Experience in patch-clamping and intracellular calcium measurments of cardiac myocytes beneficial