Articles in PresS. Am J Physiol Heart Circ Physiol (June 17, 2004). 10.1152/ajpheart.00137.2004 1
Age-dependent biochemical and contractile properties in atrium of transgenic mice overexpressing junctin
Uwe Kirchhefer 1, Hideo A. Baba 3, Gabriela Hanske 1, Larry R. Jones 4, Paulus Kirchhof 2, Wilhelm Schmitz 1, Joachim Neumann 1
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Institut für Pharmakologie und Toxikologie, 2 Medizinische Klinik und Poliklinik C,
Westfälische Wilhelms-Universität, 48149 Münster, Germany, 3
Institut für Pathologie, Universität Essen, 45147 Essen, Germany,
and 4 Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202.
Correspondence to Uwe Kirchhefer, Institut für Pharmakologie und Toxikologie, Westfälische Wilhelms-Universität, Domagkstr. 12, 48149 Münster, Germany Tel.: 0049-251-8355510; Fax: 0049-251-8355501 E-mail:
[email protected]
Copyright © 2004 by the American Physiological Society.
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RUNNING TITLE Overexpression of junctin in atria
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SUMMARY Junctin is a transmembrane protein of the cardiac junctional sarcoplasmic reticulum (SR) that binds to the ryanodine receptor, calsequestrin, and triadin 1. This quaternary protein complex is thought to facilitate the SR Ca2+ release. To improve our understanding of the contribution of junctin to the regulation of SR function, we examined the age-dependent effects of junctin overexpression in atrium of 3-, 6-, and 18-week-old transgenic mice. The ratio of atrial weight and body weight was unchanged between junctin-overexpressing (JCN) and wild-type (WT) mice at all ages investigated (n = 6-8). The protein expression of triadin 1 was decreased starting in 3-week-old JCN atria (by 69%), whereas the expression of the ryanodine receptor was diminished in 6-week-old (by 48%) and 18-week-old (by 57%) JCN atria compared to age-matched WT atria. Force of contraction was decreased by 35% in 18-week-old JCN compared to age-matched WT left atrial muscle strips which was accompanied by a prolonged time of relaxation (48.1 ± 0.9 vs. 44.2 ± 0.8 ms, resp., n = 6-8), p
