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Transcript
P26
Purpose: Heart failure is associated with
images of Di-8-ANEPPS stained myocytes.
reduced sarco/endoplasmic reticulum cal-
Specifically, Fourier analysis indicated
cium ATPase (Serca) function. Recent stud-
a maintained organization of t-tubules
ies of mice with conditional cardiomyocyte-
which transversely spanned the cell, but
Oslo, Norway
specific knockout of the Serca2 gene (KO)
an increased presence of tubules in the
Center for Heart Failure Research,
revealed that major reductions in Serca2
longitudinal direction. Immunocytochemi-
and SR function are compensated by en-
cal data showed that the newly grown lon-
hanced Ca2+ cycling over the cell mem-
gitudinal t-tubules did not contain L-type
brane. These compensations maintain
Ca2+ channels. However they contained
cardiac function at near-normal values, at
Na+/Ca2+-exchangers
least in the short term. We hypothesize that
ryanodine receptors in the sarcoplasmic
increased trans-sarcolemmal Ca2+ fluxes
reticulum. These alterations were asso-
are facilitated by alterations in sarcolemmal
ciated with increased expression of the
morphology.
L-type Ca2+ channel (α ıC subunit = ı78% of
Swift F,
Enger UH, Jølle GF, Andersson KB,
Christensen G, Sejersted OM, Louch WE
Institute for Experimental Medical Research,
Oslo University Hospital, Ullevål,
T-tubule proliferation facilitates transsarcolemmal Ca2+ flux to compensate for
declining SR function in Serca2 KO mice
University of Oslo, Norway
with
co-localized
FF values) and Na+/Ca2+-exchanger (NCXı
Methods: Ventricular cardiomyocytes were
= 2ı6% FF). Peak L-type Ca2+ currents and
isolated from KO hearts 7 weeks following
NCX-mediated Ca2+ extrusion were also
gene disruption. Serca2 flox-flox (FF) mice
enhanced in KO. Electron micrographs
served as controls. Myocyte structure and
of fixed heart sections showed reduced
electrophysiology were examined by stand-
volume of the SR after KO.
ard immunocytochemical and patch clamp
techniques.
Conclusions: Our observations indicate
that proliferation of longitudinal t-tubules
Results: Although cardiomyocyte dimen-
facilitates trans-sarcolemmal Ca2+ flux to
sions were unaltered in KO compared to
compensate for declining SR function
FF control values, total surface area was
following Serca2 KO.
increased (cell capacitance = ı82 pF vs ı47
pF, P<0.05). This resulted from increased
t-tubule density, as revealed by confocal
8th Annual CHFR Symposium
September 31 – October 01, 2010
Holmenkollen Park Hotel Rica
Oslo, Norway
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