Abstract
Development of novel therapeutic strategies for congestive heart failure
(CHF) seems to be hampered by insufficient knowledge of the molecular
machinery of excitation-contraction (EC) coupling in both normal
and failing hearts. Cardiac hypertrophy and failure represent a multitude
of cardiac phenotypes, and available invasive and non-invasive techniques,
briefly reviewed here, allow proper quantification of myocardial
function in experimental models even in rats and mice. Both reduced
fractional shortening and reduced velocity of contraction characterize
myocardial failure. Only when myocardial function is depressed in
vivo can meaningful studies be done in vitro of contractility and
EC coupling. Also, we point out potential limitations with the whole
cell patch clamp technique. Two main factors stand out as explanations
for myocardial failure. First, a basic feature of CHF seems to be
a reduced Ca$^2+$ load of the sarcoplasmic reticulum (SR) mainly
due to a low phosphorylation level of phospholamban. Second, there
seems to be a defect of the trigger mechanism of Ca$^2+$ release
from the SR. We argue that this defect only becomes manifest in the
presence of reduced Ca$^2+$ reuptake capacity of the SR and that
it may not be solely attributable to reduced gain of the Ca$^2+$-induced
Ca$^2+$ release (CICR). We list several possible explanations
for this defect that represent important avenues for future research.
- 12509477
- animals,
- antibodies,
- antibody
- blotting,
- calcium
- calcium,
- cardiac,
- cardiomegaly,
- cells,
- channel,
- channels,
- comparative
- confocal,
- congestive,
- contraction,
- cultured,
- direct,
- exchanger,
- failure,
- fluorescent
- formamides,
- gov't,
- heart
- humans,
- immunoelectron,
- immunohistochemistry,
- infarction,
- l-type,
- membrane
- microscopy,
- microtubules,
- monoclonal,
- myocardial
- myocardium,
- myocytes,
- non-u.s.
- p.h.s.,
- patch-clamp
- potentials,
- rabbits,
- rats,
- receptor
- release
- research
- ryanodine
- sarcolemma,
- sodium,
- sodium-calcium
- study,
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