HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 13/2/139    most recent 00107.2002v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Pall, G. S. Articles by Smith, G. L. Search for Related Content PubMed PubMed Citation Articles by Pall, G. S. Articles by Smith, G. L.

Abnormal contractile activity and calcium cycling in cardiac myocytes isolated from dmpk knockout mice

¹ Division of Molecular Genetics, Faculty of Biomedical and Life Sciences, Anderson College, University of Glasgow 56 Dumbarton Road, Glasgow G11 6NU
² Division of Neuroscience and Biomedical Systems, Faculty of Biomedical and Life Sciences, West Medical Building, University of Glasgow, University Avenue, Glasgow G12 8QQ, Scotland, United Kingdom

Dysfunction of the gene encoding DMPK (myotonic dystrophy protein kinase) has been implicated in the human neuromuscular disease myotonic dystrophy (DM1). The cardiac features of the disease include progressive conduction defects and ventricular arrhythmias. These defects have been observed in hearts of mice deficient for DMPK function. We have investigated the role of DMPK in the function of ventricular cardiomyocytes using dmpk knockout (KO) mice. A deficit in DMPK caused enhanced basal contractility of single cardiomyocytes and an associated increase in intracellular Ca²⁺, measured using fura-2. Biochemical measurements indicated hyperphosphorylation of phospholamban (PLB) in KO mice. This suggests increased Ca²⁺ uptake into the sarcoplasmic reticulum (SR) as the underlying cause of enhanced contractility. This conclusion was supported by the larger amplitude of caffeine-induced Ca²⁺ release from the SR in KO cardiomyocytes. Concurrent with hyperphosphorylated PLB, the response to isoprenaline was reduced. These observations suggest dmpk has a modulatory role in the control of intracellular Ca²⁺ concentration in mouse ventricular cardiomyocytes, loss of which may contribute to cardiac dysfunction in DM1.

myotonic muscular dystrophy; protein kinase; transgenic model; cardiac defect

This article has been cited by other articles:

				P. Kaliman, D. Catalucci, J. T. Lam, R. Kondo, J. C. P. Gutierrez, S. Reddy, M. Palacin, A. Zorzano, K. R. Chien, and P. Ruiz-Lozano Myotonic Dystrophy Protein Kinase Phosphorylates Phospholamban and Regulates Calcium Uptake in Cardiomyocyte Sarcoplasmic Reticulum J. Biol. Chem., March 4, 2005; 280(9): 8016 - 8021. [Abstract] [Full Text] [PDF]

				S. M. Lieberman, T. Takaki, B. Han, P. Santamaria, D. V. Serreze, and T. P. DiLorenzo Individual Nonobese Diabetic Mice Exhibit Unique Patterns of CD8+ T Cell Reactivity to Three Islet Antigens, Including the Newly Identified Widely Expressed Dystrophia Myotonica Kinase J. Immunol., December 1, 2004; 173(11): 6727 - 6734. [Abstract] [Full Text] [PDF]

				D. F. O'Cochlain, C. Perez-Terzic, S. Reyes, G. C. Kane, A. Behfar, D. M. Hodgson, J. A. Strommen, X.-K. Liu, W. van den Broek, D. G. Wansink, et al. Transgenic overexpression of human DMPK accumulates into hypertrophic cardiomyopathy, myotonic myopathy and hypotension traits of myotonic dystrophy Hum. Mol. Genet., October 1, 2004; 13(20): 2505 - 2518. [Abstract] [Full Text] [PDF]