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Laboratory of Lothar A. Blatter, MD, Dr. med.

Cardiac physiology

Blatter’s research group investigates control of intracellular calcium and its role in the regulation of excitation-contraction and excitation-transcription coupling in cells of the cardiovascular system.

Our work

Our research work focuses on Ca regulation and signaling in the heart and the cardiovascular system. It includes fundamental characterization of ion transporters and channels, electrophysiology, excitation-contraction coupling, redox signaling, mitochondrial Ca signaling and energetics, excitation-transcription coupling and changes in Ca signaling in cardiac disease (arrhythmia, hypertrophy and heart failure). Our research efforts have resulted in seminal contributions to the understanding of the spatio-temporal organization of cardiac Ca signals ranging from global Ca transients, arrhythmogenic Ca waves and Ca alternans to the elementary Ca release events from ryanodine receptor (Ca sparks and blinks) and IP3 receptor (Ca blips and puffs) Ca release channels.

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Technology

  • High-resolution single- and two-photon confocal and TIRF fluorescence imaging for simultaneous measurements of dynamic [Ca] changes in three different cellular compartments (cytosol, SR and mitochondria)
  • Electrophysiology (whole-cell patch clamp technique, single RyRs in bilayer)
  • Cell shortening measurements
  • Photolysis of caged compounds at near diffraction limited resolution
  • Biochemistry (Western blot analysis)
  • Immunocytochemistry
  • Transgenic mice models
  • Genetic engineering (adenoviral expression of Ca handling proteins and biosensors)
  • Intact heart studies
  • Seahorse flux analyzer to investigate mitochondrial respiration and metabolism

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Blatter laboratory

Publications

High-profile publications

Murphy T.H., Baraban J.M., Wier W.G. and Blatter L.A. (1994). “Visualization of Quantal Synaptic Transmission by Dendritic Calcium Imaging.” Science. 263, 529-532. PMID: 7904774

Tsugorka A., Rios E. and Blatter L.A. (1995). “Imaging Elementary Events of Calcium Release in Skeletal Muscle Cells.” Science. 269, 1723-1726. PMID: 7569901

Blatter L. A., Hüser J. and Rios E. (1997). “Sarcoplasmic Reticulum Ca2+ Release Flux Underlying Ca2+ Sparks in Cardiac Muscle.” Proc. Natl. Acad. Sci. 94, 4176-4181. PMID: 9108125

Cherednichenko G., Zima A.V., Feng W., Schaefer S., Blatter L.A. and Pessah I.N. (2004). “NADH Oxidase Activity of Rat Cardiac Sarcoplasmic Reticulum Regulates Calcium-Induced Calcium Release.” Circ. Res. 94, 478-486. (Editorial comment in Circ. Res. 94: 418, 2004). PMID: 1469901

Zima A.V. and Blatter L.A. (2004). “Inositol-1,4,5-Trisphosphate-Dependent Ca2+ Signaling in Atrial Excitation-Contraction Coupling and Arrhythmias.” J. Physiol. 555: 607-615. (Reprinted in “The Journal of Physiology: Classic Papers in Cardiovascular Physiology,” November 1, 2013). PMID: 14754996

Domeier T.L., Zima A.V., Maxwell J.T., Huke S., Mignery G.A. & Blatter L.A. (2008). “IP3 Receptor-Dependent Ca2+ Release Modulates Excitation-Contraction Coupling in Rabbit Ventricular Myocytes.” Am. J. Physiol. 294(2): H596-H604.(Editorial comment in Am. J. Physiol. 294(2): H579-581, 2008).(Highlighted in Physiology 23: 61-63, 2008). PMID: 18055509

Dedkova E.N. and Blatter L.A. (2009). “Characteristics and Function of Cardiac Mitochondrial Nitric Oxide Synthase.“ J. Physiol. 587.4, 851-872. (Highlighted in a Journal Club discussion in J. Physiol. 2009 587:2719-2720). PMID: 19103678

Domeier T.L., Blatter L.A. and Zima A.V. (2009). “Alteration of Sarcoplasmic Reticulum Ca2+ Release Termination by Ryanodine Receptor Sensitization and in Heart Failure.” J. Physiol. 587 (Pt 21), 5197-5209. (Editorial comment in J. Physiol. 587(Pt 21): 5003-5004, 2009). PMID: 19736296

Florea S.M. and Blatter L.A. (2010). “The Role of Mitochondria for the Regulation of Cardiac Alternans.” Front. Physiol. 1:141. doi: 10.3389/fphys.2010.00141. (Editorial comment in Front. Physio. 1:163. doi: 10.3389/fphys.2010.00163). PMID: 21423381

Zima A.V, Bovo E., Bers D.M. and Blatter L.A. (2010). “Ca2+ Spark-Dependent and -Independent Sarcoplasmic Reticulum Ca2+ Leak in Normal and Failing Rabbit Ventricular Myocytes.” J. Physiol. 588, 4743-4757. (Editorial comment in J. Physiol. 588: 4849, 2010; evaluated by Faculty of 1000, F1000; reprinted in “The Journal of Physiology: Biophysics and Beyond,” January 20, 2012). PMID: 20962003

Bovo E., Mazurek S.R., Blatter L.A. and Zima A.V. (2011). “Regulation of Sarcoplasmic Reticulum Ca2+ Leak by Cytosolic Ca2+ in Rabbit Ventricular Myocytes.” J. Physiol. 589, 6039-6050. (Editorial comment in J. Physiol., 589, 5899-5900, 2011). PMID: 21986204

Figueroa L., Shkryl V.M., Zhou J., Manno C., Momotake A., Brum G., Blatter L.A., Ellis-Davies G.C.R. and Ríos E. (2012). “Synthetic Localized Calcium Transients Directly Probe Signaling Mechanisms in Skeletal Muscle.” J. Physiol. 590, 1389-1411. (Perspective in J. Physiol. 590.8, 1783, 2012; reprinted in “The Journal of Physiology: Discovery in Physiology,” April 4, 2013.). PMID: 22310315

Maxwell J.T. and Blatter L.A. (2012). “Facilitation of Cytosolic Calcium Wave Propagation by Local Calcium Uptake into the Sarcoplasmic Reticulum in Cardiac Myocytes.” J. Physiol. 590.23, 6037-6045. (Highlighted in Physiology. 27: 328, 2012). PMID: 22988145

Hohendanner F., Walther S., Maxwell J.T., Kettlewell S., Awad S., Smith G.L., Lonchyna V.A. and Blatter L.A. (2015). “Inositol-1,4,5-Trisphosphate Induced Ca2+ Release and Excitation-Contraction Coupling in Atrial Myocytes from Normal and Failing Hearts.” J. Physiol. 593.6: 1459–1477. (Editorial comment in J. Physiol. 593.6: 1327-1330, 2015). PMID: 25416623

Kanaporis G. and Blatter L.A. (2015). “The Mechanisms of Calcium Cycling and Action Potential Dynamics in Cardiac Alternans.” Circ. Res. 116: 846-856. (Editorial in Circ. Res. 116: 778-780, 2015). PMID: 25532796

Blatter L.A. (2017). “The intricacies of atrial calcium cycling during excitation-contraction coupling.” J. Gen. Physiol. 149(9): 857-865. (Editorial comment in JGP 189(9): 833-836). PMID: 28798277

Maxwell J.T. & Blatter L.A. (2017). “A novel mechanism of tandem activation of ryanodine receptors by cytosolic and SR luminal Ca during excitation-contraction coupling in atrial myocytes.” J. Physiol. 595.12: 3835–3845. (Editorial comment in J. Physiol. 595.12:3683-3684, 2017). PMID: 28028837

Martinez-Hernandez E. & Blatter L.A. (2020). “Effect of carvedilol on atrial excitation-contraction coupling, Ca2+ release and arrhythmogenicity.” Am. J. Physiol. 318: H1245–H1255. PMID: 32275472

Oropeza-Almazan Y. & Blatter L.A. (2020). “Mitochondrial calcium uniporter complex activation protects against calcium alternans in atrial myocytes.” Am. J. Physiol. 319(4):H873-H881. PMID: 32857593

Blatter L.A., Kanaporis G., Martinez-Hernandez E., Oropeza-Almazan Y. & Banach K. (2021). “Excitation-contraction coupling and calcium release in atrial muscle.” Pflügers Arch. 473(3): 317-329. PMID: 33398498

Varma D., Almeida J.F.Q., DeSantiago J., Blatter L.A. & Banach K. (2022). “Inositol 1,4,5-trisphosphate receptor - reactive oxygen signaling domain regulates excitation-contraction coupling in atrial myocytes.” J. Mol. Cell. Cardiol. 163: 147-155. PMID: 34755642

Additional research

A more complete listing of Blatter’s published work can be found on PubMed.

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Funding

Current:

  • NIH R01HL155762 (multiple PIs: Blatter, Banach), IP3 receptor, NOX2 and calcium signaling domains in atrial physiology and pathophysiology
  • NIH R01HL164453 (multiple PIs: Blatter, Banach), Atrial excitation-contraction coupling, calcium signaling and electro-mechanical alternans
  • American Heart Association, post-doctoral fellowship; Recipient: Maria Yuriana Oropeza-Almazan (Sponsor: Lothar A. Blatter), Mitochondrial calcium signaling, ROS production and atrial alternans

Completed:

  • NIH R01HL134781 (PI: Blatter), Pathophysiological regulation of atrial myocyte excitation-contraction coupling and calcium signaling
  • NIH R01HL132871 (multiple PIs: Blatter, Banach), Pathophysiological regulation of atrial alternans and atrial fibrillation
  • NIH R01HL057832 (multiple PIs: Fill, Blatter, Chen), Limiting pathological calcium induced calcium release in heart
  • NIH P01HL080101 (Blatter, Project leader), Ca and InsP3 receptor signaling in cardiac myocytes
  • NIH R01HL101235 (Blatter, multiple principal investigators), Mitochondrial dysfunction in cardiac hypertrophy and failure
  • NIH R01HL062231 (PI: Blatter), E-C coupling and Ca2+ regulation in atrial myocytes
  • Leducq Foundation Transatlantic Network (Blatter, Associate Member), Redox and nitrosative regulation of cardiac remodeling: novel therapeutic approaches for heart failure

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Our team

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Contact

Lothar A. Blatter, MD, Dr. med.
Professor

Rush University
Department of Physiology & Biophysics
Jelke Building
1750 W. Harrison St., Room 1422
Chicago, IL 60612

Phone: (312) 563-3238
Fax: (312) 942-8711
Email: lothar_blatter@rush.edu

Laboratory

1312-1316, 1401 Jelke Building
1750 W. Harrison St.
Chicago, IL 60612

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