Аннотация
Altered sarcoplasmic reticulum (SR) Ca$^2+$-ATPase and Na$^+$-Ca$^2+$
exchange (NCX) function have been implicated in depressing SR Ca$^2+$
content and contractile function in heart failure (HF). Enhanced
diastolic ryanodine receptor (RyR) leak could also lower SR Ca$^2+$
load in HF, but direct cellular measurements are lacking. In this
study, we measure SR Ca$^2+$ leak directly in intact isolated
rabbit ventricular myocytes from a well-developed nonischemic HF
model. Abrupt block of SR Ca$^2+$ leak by tetracaine shifts Ca$^2+$
from the cytosol to SR. The tetracaine-induced decline in Ca$^2+$i
and increase total SR Ca$^2+$ load (Ca$^2+$SRT) directly
indicate the SR Ca$^2+$ leak (before tetracaine). Diastolic SR
Ca$^2+$ leak increases with Ca$^2+$SRT, and for any Ca$^2+$SRT
is greater in HF versus control. Mathematical modeling was used to
compare the relative impact of alterations in SR Ca$^2+$ leak,
SR Ca$^2+$-ATPase, and Na$^+$-Ca$^2+$ exchange on SR
Ca$^2+$ load in HF. We conclude that increased diastolic SR Ca$^2+$
leak in HF may contribute to reductions in SR Ca$^2+$ content,
but changes in NCX in this HF model have more impact on Ca$^2+$SRT.
- 12946948
- action
- animals,
- calcium
- calcium,
- cardiac,
- cardiovascular,
- cell
- computer
- congestive,
- contraction,
- cytosol,
- failure,
- gov't,
- heart
- humans,
- ion
- membrane
- membrane,
- models,
- myocardial
- myocardium,
- myocytes,
- non-u.s.
- p.h.s.,
- potentials,
- rabbits,
- research
- reticulum,
- sarcoplasmic
- signaling,
- simulation,
- support,
- tetracaine,
- transport,
- u.s.
- ventricles,
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