Functional properties of transgenic mouse hearts overexpressing both calsequestrin and the Na(+)-Ca(2+) exchanger
| Autor: | B, Linck, P, Bokník, S, Huke, U, Kirchhefer, J, Knapp, H, Lüss, F U, Müller, J, Neumann, Z, Tanriseven, U, Vahlensieck, H A, Baba, L R, Jones, K D, Philipson, W, Schmitz |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Calcium Channels L-Type Myocardium Body Weight Gene Expression Cardiomegaly Heart Mice Transgenic Calcium-Transporting ATPases Organ Size In Vitro Techniques Myocardial Contraction Sodium-Calcium Exchanger Mice Sarcoplasmic Reticulum Cytosol Heart Rate Caffeine Animals Calsequestrin Calcium Female RNA Messenger |
| Zdroj: | The Journal of pharmacology and experimental therapeutics. 294(2) |
| ISSN: | 0022-3565 |
| Popis: | Overexpression of calsequestrin (CSQ) induces severe cardiac hypertrophy, whereas overexpression of Na(+)-Ca(2+) exchanger (NCX) does not affect cardiac weight. To investigate a possible beneficial effect of NCX in hypertrophy, we produced transgenic mice overexpressing both NCX and CSQ (NCX/CSQ). Surprisingly, these mice developed severe heart failure. The heart/body weight ratio was enhanced and the mRNA expression of ANF, as a marker of hypertrophy, was highest in double transgenic mice. In isolated muscle strips, the basal relaxation time was prolonged in CSQ and NCX/CSQ mice. Moreover, in the presence of caffeine, force of contraction was increased only in CSQ and NCX/CSQ and was accompanied by elevated diastolic tension. In some respects, however, additional overexpression of NCX altered the CSQ phenotype into the wild-type phenotype. The expression of sarcoplasmic reticulum (SR)-Ca(2+)-ATPase and phospholamban, proteins involved in the Ca(2+) uptake of the SR, were only increased in CSQ, indicating a possible influence of NCX in the regulation of SR-Ca(2+) uptake proteins. The Ca(2+) transients and the L-type Ca(2+) currents in the presence of caffeine were very large in CSQ, but smaller increases were noted in double transgenic mice. Therefore, the successful co-overexpression of CSQ and NCX in these mice provides a novel model in which to investigate the interaction of proteins tightly linked to maintain Ca(2+) homeostasis. |
| Databáze: | OpenAIRE |
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