Abstract
Free Ca$^2+$ inside the sarcoplasmic reticulum (Ca$^2+$SR)
is difficult to measure yet critically important in controlling many
cellular systems. In cardiac myocytes, Ca$^2+$SR regulates
cardiac contractility. We directly measure Ca$^2+$SR in intact
cardiac myocytes dynamically and quantitatively during beats, with
high spatial resolution. Diastolic Ca$^2+$SR (1 to 1.5 mmol/L)
is only partially depleted (24\% to 63\%) during contraction. There
is little temporal delay in the decline in Ca$^2+$SR at release
junctions and between junctions, indicating rapid internal diffusion.
The incomplete local Ca$^2+$ release shows that the inherently
positive feedback of Ca$^2+$-induced Ca$^2+$ release terminates,
despite a large residual driving force. These findings place stringent
novel constraints on how excitation-contraction coupling works in
heart and also reveal a Ca$^2+$ store reserve that could in principle
be a therapeutic target to enhance cardiac function in heart failure.
- 12855669
- action
- adrenergic
- animals,
- beta-agonists,
- caffeine,
- calcium
- calcium,
- cardiac,
- cardiovascular,
- cell
- cells,
- computer
- congestive,
- contraction,
- cultured,
- cytosol,
- electric
- failure,
- gov't,
- heart
- humans,
- ion
- isoproterenol,
- membrane
- membrane,
- models,
- myocardial
- myocardium,
- myocytes,
- non-u.s.
- p.h.s.,
- potentials,
- rabbits,
- research
- reticulum,
- sarcoplasmic
- signaling,
- simulation,
- stimulation,
- support,
- tetracaine,
- transport,
- u.s.
- ventricles,
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