Altered mechanical properties and intracellular calcium signaling in cardiomyocytes from annexin 6 null-mutant mice

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Guojie SongS E Moss

Abstract

Annexin 6 is one of a widely expressed family of calcium-binding proteins found in most mammalian tissues, including the heart. Several studies have implicated annexin 6 in the regulation of intracellular Ca2+ signaling, and it has been shown in vitro to act as a modulator of the sarcoplasmic reticulum Ca2+-release channel, cardiac L-type calcium channel, and Na+/Ca2+ exchanger. To investigate the role of annexin 6 in intact cardiomyocytes, we used mice containing a targeted disruption of the annexin 6 gene. Compared with controls, the myocytes of annexin 6 null-mutant mice demonstrated a significant increase in the rates of shortening and relengthening. Intracellular Ca2+ transients in fura-2-loaded cardiomyocytes induced by caffeine showed a normal baseline and amplitude, whereas the rate of decay was doubled in annexin 6-/- myocytes compared with control mice. These results show that annexin 6 knockout in the mouse leads to an increase in myocyte contractility and faster diastolic Ca2+ removal from the cytoplasm. In light of published findings showing annexin 6 to be down-regulated in end-stage heart failure, these results are consistent with a role for annexin 6 as a negative inotropic factor in the regulation of cardiomyoc...Continue Reading

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Citations

Apr 24, 2009·The Journal of Biological Chemistry·Katia MonastyrskayaAnnette Draeger
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