Differential regulation of SR calcium transporters by thyroid hormone in rat atria and ventricles
Abstract
Thyroid hormone exerts positive inotropic effects on the heart mediated in part by its regulation of calcium transporter proteins, including sarco(endo)plasmic reticulum Ca 2+-ATPase (SERCA2), phospholamban (PLB), and Na+/Ca 2+ exchanger (NCX). To further understand the potential cardiac chamber-specific effects of thyroid hormone action, we compared the triiodo-l-thyronine (T 3) responsiveness of calcium transporter proteins in atrial versus ventricular tissues. Rats were rendered hypothyroid by ingestion of propylthiouracil, and a subgroup of animals was treated with T 3 for 7 days (7 μg/day by constant infusion). Atrial and left ventricular (LV) tissue homogenates were analyzed for expression of SERCA2, PLB, and NCX proteins by Western blot analysis. SERCA2 protein significantly decreased by 50% in hypothyroid LV and was normalized by T 3 treatment. In contrast, SERCA2 protein in atria was unaltered in the hypothyroid state. PLB protein expression significantly increased by 1.6- and 5-fold in the hypothyroid LV and atria, respectively, and returned to euthyroid levels with T 3 treatment. Expression of NCX protein showed a greater response to T 3 treatment in atria tissue than in ventricular tissue. Sarcoplasmic reticulum calcium cycling is determined in part by the ratio of SERCA2 to PLB. This ratio was sixfold higher in the atria compared with LV, suggesting that PLB may play a minor role in the regulation of SERCA2 function in normal atria. We conclude that calcium transporter proteins are responsive to thyroid hormone in a chamber-specific manner, with atria showing a greater change in protein content in response to T 3. The differential effect on atria may account for the occurrence of atrial rather than ventricular arrhythmias in response to even mild degrees of thyrotoxicosis.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Hypothyroidism in rats also induces changes in calcium handling.
“there are also reports that indicate hypothyroidism also induces changes in calcium handling (Cernohorsky, Kolar, Pelouch, Korecky, & Vetter, 1998; Kiss, Jakab, Kranias, & Edes, 1994; Shenoy, Klein, & Ojamaa, 2001)”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Shenoy, et al., 2001
Cites
Thyroid hormone and the cardiovascular system.
Klein, I., & Ojamaa, K. (2001) · New England Journal of Medicine · doi:10.1056/nejm200102153440707 · Cited by 2,300 · see citing works
Self-citationExcitation-Contraction Coupling and Cardiac Contractile Force
Bers, D. M., & Zhu, Y. (2010) · Journal of Cardiovascular Disease Research · doi:10.1016/s0975-3583(10)11011-0 · Cited by 1,606 · see citing works
Excitation-Contraction Coupling and Cardiac Contractile Force
Bers, D. M. (1993) · Developments in cardiovascular medicine · doi:10.1007/978-94-017-1512-6 · Cited by 777 · see citing works
Luo, W., Grupp, I. L., Harrer, J. M., Ponniah, S., Grupp, G., Duffy, J. J., Doetschman, T., & Kranias, E. G. (1994) · Circulation Research · doi:10.1161/01.res.75.3.401 · Cited by 706 · see citing works
Gene expression of the cardiac Na(+)-Ca2+ exchanger in end-stage human heart failure.
Studer, R., Reinecke, H., Bilger, J., Thomas Eschenhagen, A., Böhm, M., Hasenfuss, G. P., Just, H., Holtz, J., & Drexler, H. (1994) · Circulation Research · doi:10.1161/01.res.75.3.443 · Cited by 633 · see citing works
Izumo, S., Nadal-Ginard, B., & Mahdavi, V. (1986) · Science · doi:10.1126/science.3945800 · Cited by 621 · see citing works
The Molecular Basis of Thyroid Hormone Action
Epstein, F. H., & Brent, G. A. (1994) · New England Journal of Medicine · doi:10.1056/nejm199409293311306 · Cited by 528 · see citing works
WLuo, LGrupp, I., JHarrer, SPonniah, GGrupp, JDuffy, J., TDoetschman, & GKranias, E. (1994) · Circulation Research · Cited by 403 · see citing works
Pogwizd, S. M., Qi, M., Yuan, W., Samarel, A. M., & Bers, D. M. (1999) · Circulation Research · doi:10.1161/01.res.85.11.1009 · Cited by 399 · see citing works
Phospholamban: A Prominent Regulator of Myocardial Contractility
Koss, K. L., & Kranias, E. G. (1996) · Circulation Research · doi:10.1161/01.res.79.6.1059 · Cited by 355 · see citing works
Biochemical basis of thyroid hormone action in the heart.
Dillmann, W. H. (1990) · The American Journal of Medicine · doi:10.1016/0002-9343(90)90530-q · Cited by 338 · see citing works
Kadambi, V. J., Ponniah, S., Harrer, J. M., Hoit, B. D., Dorn, G. W., Walsh, R. A., & Kranias, E. G. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118446 · Cited by 327 · see citing works
He, H., Giordano, F. J., Hilal-Dandan, R., Choi, D. J., Rockman, H. A., McDonough, P. M., Bluhm, W. F., Meyer, M., Sayen, M. R., Swanson, E., et al. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119544 · Cited by 323 · see citing works
Kiss, E., Jakab, G., Kranias, E. G., & Edes, I. (1994) · Circulation Research · doi:10.1161/01.res.75.2.245 · Cited by 263 · see citing works
Hormonal modulation of a gene injected into rat heart in vivo.
Kitsis, R. N., Buttrick, P. M., McNally, E. M., Kaplan, M. L., & Leinwand, L. A. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.10.4138 · Cited by 176 · see citing works
Mintz, G. L., Pizzarello, R. A., & Klein, I. L. (1991) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-73-1-146 · Cited by 156 · see citing works
Self-citationTsika, R. W., Bahl, J. J., Leinwand, L. A., & Morkin, E. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.1.379 · Cited by 146 · see citing works
Regulation of Rat Cardiac Kv1.5 Gene Expression by Thyroid Hormone Is Rapid and Chamber Specific
Ojamaa, K., Sabet, A., Kenessey, Á., Shenoy, R., & Klein, I. L. (1999) · Endocrinology · doi:10.1210/endo.140.7.6776 · Cited by 106 · see citing works
Self-citationThyroid hormone regulation of phospholamban phosphorylation in the rat heart
Ojamaa, K., Kenessey, A., & Klein, I. (2000) · Endocrinology · doi:10.1210/endo.141.6.7514 · Cited by 106 · see citing works
Self-citationThyroid hormone and hemodynamic regulation of beta-myosin heavy chain promoter in the heart
Ojamaa, K., Klemperer, J. D., MacGilvray, S. S., Klein, I. L., & Samarel, A. M. (1996) · Endocrinology · doi:10.1210/endo.137.3.8603588 · Cited by 85 · see citing works
Self-citationReed, T. D., Babu, G. J., Ji, Y. H., et al. (2000) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1999.1095 · Cited by 83 · see citing works
Thyroid Hormone–Induced Alterations in Phospholamban-Deficient Mouse Hearts
Kiss, É., Brittsan, A. G., Edes, I. F., Grupp, I. L., Grupp, G., & Kranias, E. G. (1998) · Circulation Research · doi:10.1161/01.res.83.6.608 · Cited by 78 · see citing works
Gaughan, J. P., Furukawa, S., Jeevanandam, V., et al. (1999) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1999.277.2.h714 · Cited by 78 · see citing works
Gustafson, T. A., Markham, B. E., Bahl, J. J., et al. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.10.3122 · Cited by 76 · see citing works
Differential Phospholamban Gene Expression in Murine Cardiac Compartments
Koss, K. L., Ponniah, S., Jones, W. K., et al. (1995) · Circulation Research · doi:10.1161/01.res.77.2.342 · Cited by 62 · see citing works
Thyroid control of sarcolemmal Na+/Ca2+exchanger and SR Ca2+-ATPase in developing rat heart
Cernohorský, J., Kolář, F., Pelouch, V., KORECKY, B., & Vetter, R. (1998) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1998.275.1.h264 · Cited by 61 · see citing works
Time course of the in vivo effects of thyroid hormone on cardiac gene expression
Balkman, C. E., Ojamaa, K., & Klein, I. L. (1992) · Endocrinology · doi:10.1210/endo.130.4.1312435 · Cited by 59 · see citing works
Self-citationHolt, E., Sjaastad, I., Lunde, P., Christensen, G., & Sejersted, O. M. (1999) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1998.0900 · Cited by 51 · see citing works
Translation of Ser16 and Thr17 phosphorylation of phospholamban into Ca2+-pump stimulation
Jackson, W. A., & Colyer, J. (1996) · Biochemical Journal · doi:10.1042/bj3160201 · Cited by 49 · see citing works
Boerth, S. R., & Artman, M. (1996) · Cardiovascular Research · doi:10.1016/s0008-6363(95)00160-3 · Cited by 48 · see citing works
Identification of a Contractile-responsive Element in the Cardiac α-Myosin Heavy Chain Gene
Ojamaa, K., Samarel, A. M., & Klein, I. L. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.52.31276 · Cited by 48 · see citing works
Self-citationIn vivo regulation of recombinant cardiac myosin heavy chain gene expression by thyroid hormone.
Ojamaa, K., & Klein, I. L. (1993) · Endocrinology · doi:10.1210/endo.132.3.8440168 · Cited by 45 · see citing works
Self-citationKaasik, A. (1997) · Cardiovascular Research · doi:10.1016/s0008-6363(97)00069-2 · Cited by 32 · see citing works
Changes in Thyroid State Affect pHiand Nai+Homeostasis in Rat Ventricular Myocytes
Wolska, B. M., Averyhart‐Fullard, V., Omachi, A., Stojanović, M. O., Kallen, R. G., & Solaro, R. J. (1997) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1997.0495 · Cited by 29 · see citing works
Xiao, Q., & Ojamaa, K. (1998) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1997.0574 · Cited by 18 · see citing works
Self-citationThyroid hormones differentially affect sarcoplasmic reticulum function in rat atria and ventricles
Kaasik, A., Minajeva, A., Paju, K., Eimre, M., & Seppet, E. K. (1997) · Springer eBooks · doi:10.1007/978-1-4615-5765-4_16 · Cited by 17 · see citing works
Thyroid hormones differentially affect sarcoplasmic reticulum function in rat atria and ventricles
Kaasik, A., Minajeva, A., Paju, K., Eimre, M., & Seppet, E. K. (1997) · Molecular and Cellular Biochemistry · doi:10.1023/a:1006887231150 · Cited by 16 · see citing works
Organic Particles in the Ocean
Hobson, L. A., & Weyl, P. K. (1968) · Science · doi:10.1126/science.162.3853.587 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Small and large animal models in cardiac contraction research: advantages and disadvantages
Milani-Nejad, N., & Janssen, P. M. L. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.10.007 · Cited by 484 · see citing works
Chaudhary, K. W., Rossman, E. I., Piacentino, V., Kenessey, A., Weber, C., Gaughan, J. P., Ojamaa, K., Klein, I., Bers, D. M., Houser, S. R., et al. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2004.05.049 · Cited by 95 · see citing works
Self-citation
- Authors
- Shenoy, R., Klein, I., & Ojamaa, K.
- Affiliations
- Northwell Health (US)
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2001-10-01
- Volume
- 281
- Issue
- 4
- Pages
- H1690-H1696
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- OpenAlex
- W2326962210
- Cited by
- 65
- References
- 38
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 5 · 2015: 1 · 2014: 4 · 2013: 3 · 2012: 4
- FWCI
- 2.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl058849-03)
- National Heart, Lung, and Blood Institute (R01HL056804, HL-56804, HL58849)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- thyroid hormones, triiodothyronine, calcium transporters, SERCA2, phospholamban, Na+/Ca2+ exchanger, atrium, left ventricle, hypothyroidism, propylthiouracil, sarcoplasmic reticulum calcium cycling, thyrotoxicosis, atrial arrhythmias, positive inotropic effect
- MeSH terms
- Phospholamban, Calcium-Transporting ATPases, Animals, Biological Transport, Calcium, Calcium-Binding Proteins, Heart Atria, Heart Ventricles, Male, Myocardium, RNA, Messenger, Sarcoplasmic Reticulum, Triiodothyronine, Blotting, Western, Rats, Sprague-Dawley, Myosin Heavy Chains, Rats, Sarcoplasmic Reticulum Calcium-Transporting ATPases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
