Tpm1

Summary

Gene Symbol: Tpm1
Description: tropomyosin 1, alpha
Alias: AA986836, AI854628, TM2, TPM1kappa, Tm3, Tmpa, Tpm-1, alpha-TM, tropomyosin alpha-1 chain, alpha-tropomyosin, tropomyosin 1 kappa, tropomyosin-1
Species: mouse
Products:     Tpm1

Top Publications

  1. Jeanes A, Wilhelm D, Wilson M, Bowles J, McClive P, Sinclair A, et al. Evaluation of candidate markers for the peritubular myoid cell lineage in the developing mouse testis. Reproduction. 2005;130:509-16 pubmed
    ..Collagen type-I, inhibinbetaA, caldesmon 1 and tropomyosin 1 were found to be expressed by early-stage PM cells...
  2. Vahebi S, Ota A, Li M, Warren C, de Tombe P, Wang Y, et al. p38-MAPK induced dephosphorylation of alpha-tropomyosin is associated with depression of myocardial sarcomeric tension and ATPase activity. Circ Res. 2007;100:408-15 pubmed
    ..These data are the first to indicate that chronic activation of p38alpha MAPK directly depresses sarcomeric function in association with decreased phosphorylation of alpha-tropomyosin. ..
  3. Mastrototaro G, Liang X, Li X, Carullo P, Piroddi N, Tesi C, et al. Nebulette knockout mice have normal cardiac function, but show Z-line widening and up-regulation of cardiac stress markers. Cardiovasc Res. 2015;107:216-25 pubmed publisher
    ..These results suggest that the nebulette disease causing mutations have dominant gain-of-function effects. ..
  4. Schevzov G, Bryce N, Almonte Baldonado R, Joya J, Lin J, Hardeman E, et al. Specific features of neuronal size and shape are regulated by tropomyosin isoforms. Mol Biol Cell. 2005;16:3425-37 pubmed
    ..expression on neuronal morphogenesis, embryonic cortical neurons from transgenic mice expressing the isoforms Tm3 and Tm5NM1, under the control of the beta-actin promoter, were cultured in vitro...
  5. Schleef M, Werner K, Satzger U, Kaupmann K, Jockusch H. Chromosomal localization and genomic cloning of the mouse alpha-tropomyosin gene Tpm-1. Genomics. 1993;17:519-21 pubmed
    ..5-kb of Tpm-1. The same restriction patterns were observed, proving the identity of the mapped and the cloned gene. The identity was supported by sequencing the 3' end of the gene. ..
  6. Burkart E, Arteaga G, Sumandea M, Prabhakar R, Wieczorek D, Solaro R. Altered signaling surrounding the C-lobe of cardiac troponin C in myofilaments containing an alpha-tropomyosin mutation linked to familial hypertrophic cardiomyopathy. J Mol Cell Cardiol. 2003;35:1285-93 pubmed
    ..Although levels of phosphorylation at protein kinase C-dependent sites were the same in TG and NTG myofilaments, our data indicate that the effects of phosphorylation were more depressive in TG hearts. ..
  7. Braverman R, Cooper H, Lee H, Prasad G. Anti-oncogenic effects of tropomyosin: isoform specificity and importance of protein coding sequences. Oncogene. 1996;13:537-45 pubmed
    ..specificity in cellular transformation, cDNAs that consist of coding sequences of TM1 (product of beta gene) and TM2 (product of alpha gene), but lacking untranslated regions (UTRs), have been expressed separately in DT (v-Ki-ras ..
  8. Cohen S, Zhai B, Gygi S, Goldberg A. Ubiquitylation by Trim32 causes coupled loss of desmin, Z-bands, and thin filaments in muscle atrophy. J Cell Biol. 2012;198:575-89 pubmed publisher
    ..Thus, during fasting, desmin phosphorylation increases and enhances Trim32-mediated degradation of the desmin cytoskeleton, which appears to facilitate the breakdown of Z-bands and thin filaments...
  9. Klocke R, Augustin A, Ronsiek M, Stief A, van Der Putten H, Jockusch H. Dynamin genes Dnm1 and Dnm2 are located on proximal mouse chromosomes 2 and 9, respectively. Genomics. 1997;41:290-2 pubmed
    ..Potential relations of both loci to disease genes are discussed. ..

More Information

Publications62

  1. Nakagawa N, Hoshijima M, Oyasu M, Saito N, Tanizawa K, Kuroda S. ENH, containing PDZ and LIM domains, heart/skeletal muscle-specific protein, associates with cytoskeletal proteins through the PDZ domain. Biochem Biophys Res Commun. 2000;272:505-12 pubmed
  2. Gromak N, Rideau A, Southby J, Scadden A, Gooding C, Huttelmaier S, et al. The PTB interacting protein raver1 regulates alpha-tropomyosin alternative splicing. EMBO J. 2003;22:6356-64 pubmed
    ..This suggests a novel mechanism for PTB-mediated splicing repression involving recruitment of raver1 as a potent splicing co-repressor. ..
  3. Muthuchamy M, Pieples K, Rethinasamy P, Hoit B, Grupp I, Boivin G, et al. Mouse model of a familial hypertrophic cardiomyopathy mutation in alpha-tropomyosin manifests cardiac dysfunction. Circ Res. 1999;85:47-56 pubmed
    ..Thus, the FHC alpha-TM transgenic mouse can serve as a model system for the examination of pathological and physiological alterations imparted through aberrant TM isoforms. ..
  4. Yar S, Chowdhury S, Davis R, Kobayashi M, Monasky M, Rajan S, et al. Conserved Asp-137 is important for both structure and regulatory functions of cardiac ?-tropomyosin (?-TM) in a novel transgenic mouse model expressing ?-TM-D137L. J Biol Chem. 2013;288:16235-46 pubmed publisher
    ..Thus, our results provide insight into the link between flexibility of TM and its function in ejecting hearts. ..
  5. Yamazaki K, Mizui Y, Sagane K, Tanaka I. Assignment of a disintegrin and metalloproteinase domain 10 (Adam10) gene to mouse chromosome 9. Genomics. 1997;46:528-9 pubmed
  6. Mun J, Kensler R, Harris S, Craig R. The cMyBP-C HCM variant L348P enhances thin filament activation through an increased shift in tropomyosin position. J Mol Cell Cardiol. 2016;91:141-7 pubmed publisher
    ..We conclude that the L348P mutation causes a gain of function by enhancing tropomyosin displacement on the thin filament in a phosphorylation-independent way. ..
  7. Takenaga K, Nakamura Y, Tokunaga K, Kageyama H, Sakiyama S. Isolation and characterization of a cDNA that encodes mouse fibroblast tropomyosin isoform 2. Mol Cell Biol. 1988;8:5561-5 pubmed
    We isolated and characterized a cDNA clone encoding tropomyosin isoform 2 (TM2) from a mouse fibroblast cDNA library...
  8. Vikstrom K, Leinwand L. Contractile protein mutations and heart disease. Curr Opin Cell Biol. 1996;8:97-105 pubmed
    Mutations in several muscle structural proteins (the myosin heavy chain, alpha tropomyosin, cardiac troponin T and myosin binding protein C) result in a genetically dominant heart disease, hypertrophic cardiomyopathy...
  9. Clayton L, Johnson M. Tropomyosin in preimplantation mouse development: identification, expression, and organization during cell division and polarization. Exp Cell Res. 1998;238:450-64 pubmed
    ..We conclude that the early mouse conceptus contains a unique and specific set of tropomyosins which respond to polarizing signals. ..
  10. McMichael B, Kotadiya P, Singh T, Holliday L, Lee B. Tropomyosin isoforms localize to distinct microfilament populations in osteoclasts. Bone. 2006;39:694-705 pubmed
    ..This compartmentalization of tropomyosins to specific actin structures within osteoclasts is likely to play a critical role in determining the dynamic properties of the actin cytoskeleton and thus osteoclast activity. ..
  11. Rajan S, Ahmed R, Jagatheesan G, Petrashevskaya N, Boivin G, Urboniene D, et al. Dilated cardiomyopathy mutant tropomyosin mice develop cardiac dysfunction with significantly decreased fractional shortening and myofilament calcium sensitivity. Circ Res. 2007;101:205-14 pubmed
    ..As such, this is the first mouse model in which a mutation in a sarcomeric thin filament protein, specifically TM, leads to DCM. ..
  12. Schiaffino S, Reggiani C. Molecular diversity of myofibrillar proteins: gene regulation and functional significance. Physiol Rev. 1996;76:371-423 pubmed
    ..Both myosin and troponin isoforms contribute to the differences in the resistance to fatigue of muscle fibers...
  13. Karam C, Warren C, Rajan S, de Tombe P, Wieczorek D, Solaro R. Expression of tropomyosin-? induces dilated cardiomyopathy and depresses cardiac myofilament tension by mechanisms involving cross-bridge dependent activation and altered tropomyosin phosphorylation. J Muscle Res Cell Motil. 2011;31:315-22 pubmed publisher
    Tropomyosin-kappa (TPM1-?) is a newly discovered tropomyosin (TM) isoform that is exclusively expressed in the human heart and generated by an alternative splicing of the ?-TM gene...
  14. McKeown C, Nowak R, Gokhin D, Fowler V. Tropomyosin is required for cardiac morphogenesis, myofibril assembly, and formation of adherens junctions in the developing mouse embryo. Dev Dyn. 2014;243:800-17 pubmed publisher
    ..for tropomyosin (TM) in mammalian myofibril assembly and cardiac development by analyzing a deletion in the mouse TPM1 gene targeting ?TM1, the major striated muscle TM isoform. Mice lacking ?TM1 are embryonic lethal at E9...
  15. Lin J, Yan Y, Hsieh W, Peng P, Su C, Tarn W. RBM4 promotes pancreas cell differentiation and insulin expression. Mol Cell Biol. 2013;33:319-27 pubmed publisher
    ..These results suggest that RBM4 may have role in promoting pancreas cell differentiation and endocrine function, essentially via alternative splicing regulation. ..
  16. Nassar R, Malouf N, Mao L, Rockman H, Oakeley A, Frye J, et al. cTnT1, a cardiac troponin T isoform, decreases myofilament tension and affects the left ventricular pressure waveform. Am J Physiol Heart Circ Physiol. 2005;288:H1147-56 pubmed
  17. Rethinasamy P, Muthuchamy M, Hewett T, Boivin G, Wolska B, Evans C, et al. Molecular and physiological effects of alpha-tropomyosin ablation in the mouse. Circ Res. 1998;82:116-23 pubmed
    ..The present study suggests that translational regulation plays a major role in the control of TM expression. ..
  18. Liu X, Ramjiganesh T, Chen Y, Chung S, Hall S, SCHISSEL S, et al. Disruption of striated preferentially expressed gene locus leads to dilated cardiomyopathy in mice. Circulation. 2009;119:261-8 pubmed publisher
    ..These findings demonstrate that mutation of the Speg locus leads to cardiac dysfunction and a phenotype consistent with a dilated cardiomyopathy. ..
  19. Gaffin R, Tong C, Zawieja D, Hewett T, Klevitsky R, Robbins J, et al. Charged residue alterations in the inner-core domain and carboxy-terminus of alpha-tropomyosin differentially affect mouse cardiac muscle contractility. J Physiol. 2004;561:777-91 pubmed
    ..These data demonstrate that changing charged residues at either the inner-core domain or the carboxyl end of TM alters sarcomeric performance differently, suggesting that the function of TM is compartmentalized along its length. ..
  20. von der Ecken J, Müller M, Lehman W, Manstein D, Penczek P, Raunser S. Structure of the F-actin-tropomyosin complex. Nature. 2015;519:114-7 pubmed publisher
    ..Our results allow us to understand the role of individual mutations in the genesis of actin- and tropomyosin-related diseases and will serve as a strong foundation for the targeted development of drugs. ..
  21. Blanchard E, Iizuka K, Christe M, Conner D, Geisterfer Lowrance A, Schoen F, et al. Targeted ablation of the murine alpha-tropomyosin gene. Circ Res. 1997;81:1005-10 pubmed
    ..These findings imply that in heterozygotes there is a regulatory mechanism that maintains the level of myofibrillar tropomyosin despite the reduction in alpha-tropomyosin mRNA. ..
  22. Issa L, Palmer S, Guven K, Santucci N, Hodgson V, Popovic K, et al. MusTRD can regulate postnatal fiber-specific expression. Dev Biol. 2006;293:104-15 pubmed
    ..These data are consistent with our initial predictions for hMusTRD1alpha1 and suggest that slow fiber genes contain a specific common regulatory element that can be targeted by MusTRD proteins. ..
  23. Gaffin R, Gokulan K, Sacchettini J, Hewett T, Klevitsky R, Robbins J, et al. Changes in end-to-end interactions of tropomyosin affect mouse cardiac muscle dynamics. Am J Physiol Heart Circ Physiol. 2006;291:H552-63 pubmed
  24. Karp N, Baker L, Gerdin A, Adams N, Ramirez Solis R, White J. Optimising experimental design for high-throughput phenotyping in mice: a case study. Mamm Genome. 2010;21:467-76 pubmed publisher
    ..Consequently, in confirmatory studies, a power analysis along with the 3Rs can provide justification to increase the number of mice used. ..
  25. Bach C, Creed S, Zhong J, Mahmassani M, Schevzov G, Stehn J, et al. Tropomyosin isoform expression regulates the transition of adhesions to determine cell speed and direction. Mol Cell Biol. 2009;29:1506-14 pubmed publisher
    ..Thus, we propose that Tm5NM1 can regulate the feedback loop between focal adhesion disassembly and focal complex formation at the leading edge that is required for productive and directed cell movement. ..
  26. Dube S, Panebianco L, Matoq A, Chionuma H, Denz C, Poiesz B, et al. Expression of TPM1?, a Novel Sarcomeric Isoform of the TPM1 Gene, in Mouse Heart and Skeletal Muscle. Mol Biol Int. 2014;2014:896068 pubmed publisher
    We have investigated the expression of TPM1 ? and TPM1 ? in mouse striated muscles. TPM1 ? and TMP1 ? were amplified from the cDNA of mouse heart by using conventional RT-PCR...
  27. Ryseck R, Macdonald Bravo H, Zerial M, Bravo R. Coordinate induction of fibronectin, fibronectin receptor, tropomyosin, and actin genes in serum-stimulated fibroblasts. Exp Cell Res. 1989;180:537-45 pubmed
  28. Prabhakar R, Petrashevskaya N, Schwartz A, Aronow B, Boivin G, Molkentin J, et al. A mouse model of familial hypertrophic cardiomyopathy caused by a alpha-tropomyosin mutation. Mol Cell Biochem. 2003;251:33-42 pubmed
    ..This study demonstrates that mutations within tropomyosin can be severely disruptive of sarcomeric function, triggering a hypertrophic response coupled with a cascade of alterations in gene expression. ..
  29. Ang S, Uebersohn A, Spencer C, Huang Y, Lee J, Ge K, et al. KMT2D regulates specific programs in heart development via histone H3 lysine 4 di-methylation. Development. 2016;143:810-21 pubmed publisher
    ..Our findings indicate that KMT2D is essential for regulating cardiac gene expression during heart development primarily via H3K4 di-methylation. ..
  30. Muthuchamy M, Pajak L, Howles P, Doetschman T, Wieczorek D. Developmental analysis of tropomyosin gene expression in embryonic stem cells and mouse embryos. Mol Cell Biol. 1993;13:3311-23 pubmed
    ..Our results show for the first time that the alpha- and beta-TM striated muscle transcripts are present in the earliest functional stages of the heart, and these TM isoforms are identical to those present throughout cardiac development. ..
  31. Jaradat S, Ko M, Grossman L. Tissue-specific expression and mapping of the Cox7ah gene in mouse. Genomics. 1998;49:363-70 pubmed
    ..1. As a result, all three COX heart isoform genes in mouse group to chromosome 7. Interestingly, mapping of the mouse Cox7al to chromosome 9 suggests a new syntenic region between the mouse and the human genomes. ..
  32. Kochilas L, Li J, Jin F, Buck C, Epstein J. p57Kip2 expression is enhanced during mid-cardiac murine development and is restricted to trabecular myocardium. Pediatr Res. 1999;45:635-42 pubmed
    ..This result and further structural analysis suggests that the myocardial defect of Splotch embryos is associated with precocious cardiomyocyte differentiation. ..
  33. Nixon B, Liu B, Scellini B, Tesi C, Piroddi N, Ogut O, et al. Tropomyosin Ser-283 pseudo-phosphorylation slows myofibril relaxation. Arch Biochem Biophys. 2013;535:30-8 pubmed publisher
    ..This supports a role for Tm as a key protein in the regulation of muscle relaxation dynamics. ..
  34. Lynn M, Tal Grinspan L, Holeman T, Jimenez J, Strom J, Tardiff J. The structural basis of alpha-tropomyosin linked (Asp230Asn) familial dilated cardiomyopathy. J Mol Cell Cardiol. 2017;108:127-137 pubmed publisher
    ..families identified a novel dilated cardiomyopathy (DCM)-linked mutation in the gene coding for alpha-tropomyosin (TPM1) resulting in the substitution of an aspartic acid for an asparagine (at residue 230)...
  35. Eyre H, Akkari P, Wilton S, Callen D, Baker E, Laing N. Assignment of the human skeletal muscle alpha-tropomyosin gene (TPM1) to band 15q22 by fluorescence in situ hybridization. Cytogenet Cell Genet. 1995;69:15-7 pubmed
    A sequence-tagged site (STS) was developed for the human skeletal muscle alpha-tropomyosin gene (TPM1) and used to isolate a genomic clone, lambda TPM1.1, containing part of the TPM1 gene...
  36. Corbett M, Robinson C, Dunglison G, Yang N, Joya J, Stewart A, et al. A mutation in alpha-tropomyosin(slow) affects muscle strength, maturation and hypertrophy in a mouse model for nemaline myopathy. Hum Mol Genet. 2001;10:317-28 pubmed
    ..We suggest that the clinical phenotype is precipitated by a failure of the hypertrophy to persist and therefore compensate for muscle weakness...
  37. Delgado Olguin P, Huang Y, Li X, Christodoulou D, Seidman C, Seidman J, et al. Epigenetic repression of cardiac progenitor gene expression by Ezh2 is required for postnatal cardiac homeostasis. Nat Genet. 2012;44:343-7 pubmed publisher
    ..Our results suggest that epigenetic dysregulation in embryonic progenitor cells is a predisposing factor for adult disease and dysregulated stress responses. ..
  38. Chen J, Murchison E, Tang R, Callis T, Tatsuguchi M, Deng Z, et al. Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure. Proc Natl Acad Sci U S A. 2008;105:2111-6 pubmed publisher
    ..Together, our studies demonstrate essential roles for Dicer in cardiac contraction and indicate that miRNAs play critical roles in normal cardiac function and under pathological conditions. ..
  39. Bharadwaj S, Hitchcock DeGregori S, Thorburn A, Prasad G. N terminus is essential for tropomyosin functions: N-terminal modification disrupts stress fiber organization and abolishes anti-oncogenic effects of tropomyosin-1. J Biol Chem. 2004;279:14039-48 pubmed
    ..Our studies provide in vivo functional evidence that the N terminus is a critical determinant of TM1 functions, which in turn determines the organization of stress fibers. ..
  40. Jagatheesan G, Rajan S, Petrashevskaya N, Schwartz A, Boivin G, Arteaga G, et al. Rescue of tropomyosin-induced familial hypertrophic cardiomyopathy mice by transgenesis. Am J Physiol Heart Circ Physiol. 2007;293:H949-58 pubmed
    ..These results demonstrate that alterations in calcium response by modification of contractile proteins can prevent the pathological and physiological effects of this disease. ..
  41. Kubo E, Shibata S, Shibata T, Kiyokawa E, Sasaki H, Singh D. FGF2 antagonizes aberrant TGF? regulation of tropomyosin: role for posterior capsule opacity. J Cell Mol Med. 2017;21:916-928 pubmed publisher
    ..Stress fibre formation and up-regulation of ?-smooth muscle actin (?SMA) induced by TGF?2 could be reversed by Tpm1/2 knock-down by siRNA. Expression of Tpm1/2 and stress fibre formation induced by TGF?2 could be reversed by FGF2...
  42. Gaffin R, Gokulan K, Sacchettini J, Hewett T, Klevitsky R, Robbins J, et al. Charged residue changes in the carboxy-terminus of alpha-tropomyosin alter mouse cardiac muscle contractility. J Physiol. 2004;556:531-43 pubmed
    ..Our results provide the first evidence that charge changes at the carboxy-terminal of alpha-TM alter the functional characteristics of the heart at both the whole organ and myofilament levels. ..
  43. Geeves M, Hitchcock Degregori S, Gunning P. A systematic nomenclature for mammalian tropomyosin isoforms. J Muscle Res Cell Motil. 2015;36:147-53 pubmed publisher
    ..The National Center for Biotechnology Information (NCBI) website has been amended to include the nomenclature for the human, mouse and rat genes. ..
  44. Rubel C, Schisler J, Hamlett E, Dekroon R, Gautel M, Alzate O, et al. Diggin' on u(biquitin): a novel method for the identification of physiological E3 ubiquitin ligase substrates. Cell Biochem Biophys. 2013;67:127-38 pubmed publisher
  45. Yang W, Li C, Mansour S. Impaired motor coordination in mice that lack punc. Mol Cell Biol. 2001;21:6031-43 pubmed
    ..Compared with control littermates, however, homozygous mutants had significantly reduced retention times on the Rotarod, suggesting a role for Bergmann glia-expressed Punc in the cerebellar control of motor coordination. ..
  46. Schulz E, Correll R, Sheikh H, Lofrano Alves M, Engel P, Newman G, et al. Tropomyosin dephosphorylation results in compensated cardiac hypertrophy. J Biol Chem. 2012;287:44478-89 pubmed publisher
    ..Collectively, these results suggest that modification of the Tm phosphorylation status in the heart, depending upon the cardiac state/condition, may modulate the development of cardiac hypertrophy. ..
  47. Zhang S, Kim K, Rosén A, Smyth J, Sakuma R, Delgado Olguin P, et al. Iroquois homeobox gene 3 establishes fast conduction in the cardiac His-Purkinje network. Proc Natl Acad Sci U S A. 2011;108:13576-81 pubmed publisher
    ..Irx3 directly represses Cx43 transcription and indirectly activates Cx40 transcription. Our results reveal a critical role for Irx3 in the precise regulation of intercellular gap junction coupling and impulse propagation in the heart. ..
  48. Schulz E, Wilder T, Chowdhury S, Sheikh H, Wolska B, Solaro R, et al. Decreasing tropomyosin phosphorylation rescues tropomyosin-induced familial hypertrophic cardiomyopathy. J Biol Chem. 2013;288:28925-35 pubmed publisher
    ..This is the first study to demonstrate that decreasing phosphorylation of tropomyosin can rescue a hypertrophic cardiomyopathic phenotype. ..
  49. Wittenburg H, Lammert F, Wang D, Churchill G, Li R, Bouchard G, et al. Interacting QTLs for cholesterol gallstones and gallbladder mucin in AKR and SWR strains of mice. Physiol Genomics. 2002;8:67-77 pubmed
    ..According to standard nomenclature, the gallstone QTL on chromosome 9 is named Lith5. ..
  50. Schevzov G, Fath T, Vrhovski B, Vlahovich N, Rajan S, Hook J, et al. Divergent regulation of the sarcomere and the cytoskeleton. J Biol Chem. 2008;283:275-83 pubmed
    ..Comprehensive analyses of tissues from transgenic and knock-out mouse lines that overexpress the cytoskeletal Tms, Tm3 and Tm5NM1, and a comparison with sarcomeric Tms provide evidence for this...
  51. Schleef M, Zuhlke C, Schöffl F, Jockusch H. Subtractive cDNA cloning as a tool to analyse secondary effects of a muscle disease. Characterization of affected genes in the myotonic ADR mouse. Neuromuscul Disord. 1994;4:205-17 pubmed
    ..A cDNA derived from the 1100 nucleotide parvalbumin transcript was cloned and the sequence for the as yet unknown 3' extended trailer, generated by alternative polyadenylation, was determined. ..
  52. Chevray P, Nathans D. Protein interaction cloning in yeast: identification of mammalian proteins that react with the leucine zipper of Jun. Proc Natl Acad Sci U S A. 1992;89:5789-93 pubmed
    ..Our results illustrate the range of protein interaction cloning for discovering proteins that bind to a given target polypeptide. ..
  53. Patel J, Fitzsimons D, Buck S, Muthuchamy M, Wieczorek D, Moss R. PKA accelerates rate of force development in murine skinned myocardium expressing alpha- or beta-tropomyosin. Am J Physiol Heart Circ Physiol. 2001;280:H2732-9 pubmed
    ..These results show that PKA-mediated phosphorylation of myofibrillar proteins significantly alters the static and dynamic mechanical properties of myocardium, and these effects occur regardless of the type of Tm expressed...