Altered mechanical properties and intracellular calcium signaling in cardiomyocytes from annexin 6 null-mutant mice.
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 cardiomyocyte mechanics.
Song
Guojie
G
Division of Cell Biology, Institute of Ophthalmology, University College London, London EC1V 9EL, UK.
Harding
Sian E
SE
Duchen
Michael R
MR
Tunwell
Richard
R
O'Gara
Peter
P
Hawkins
Tim E
TE
Moss
Stephen E
SE
D000818:Animals; D017317:Annexin A6 / Q000235:genetics* / Q000502:physiology*; D001696:Biomechanical Phenomena; D002110:Caffeine / Q000494:pharmacology; D020013:Calcium Signaling; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D018390:Gene Targeting; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D008955:Models, Cardiovascular; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*
D017317:Annexin A6; D002110:Caffeine