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, 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. (Perspective in J. Physiol. 593.6: 1385–1386, 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. ( Circ. Res. 116: 778-780, 2015). PMCID: PMC4344847

Additional research

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

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Funding

Current and past (3 years)

  • 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
  • Leducq Foundation Transatlantic Network (Blatter, Associate Member): Redox and nitrosative regulation of cardiac remodeling: novel therapeutic approaches for heart failure
  • NIH R01HL062231: E-C coupling and Ca2+ regulation in atrial myocytes

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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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