Аннотация
The hypothesis of a Ca$^2+$-induced Ca$^2+$ release (CICR)
from the sarcoplasmic reticulum (SR) is supported by experiments
done in skinned cardiac cells (sarcolemma removed by microdissection).
According to this hypothesis, the transsarcolemmal Ca$^2+$ influx
does not activate the myofilaments directly but through the induction
of a Ca$^2+$ release from the SR. The stimulus gating CICR is
not a small change in free Ca$^2+$ concentration (deltafree
Ca$^2+$) outside the SR but a function of the rate of this change
(deltafree Ca$^2+$/delta t). The initial relatively fast component
of the transsarcolemmal Ca$^2+$ current would trigger Ca$^2+$
release; the subsequent slow component, perhaps corresponding to
noninactivating Ca$^2+$ channels, would load the SR with an amount
of Ca$^2+$ available for release during subsequent beats. Inactivation
of CICR is caused by the large increase of free Ca$^2+$ outside
the SR resulting from Ca$^2+$ release, which inhibits further
release. This negative feedback helps to explain that CICR is not
all or none. During relaxation the Ca$^2+$ reaccumulation in
the SR is backed up by the Ca$^2+$ efflux across the sarcolemma
through Na$^+$-Ca$^2+$ exchange and the sarcolemmal Ca$^2+$
pump. Computations of the Ca$^2+$ buffering in the mammalian
ventricular cell and of the systolic transsarcolemmal Ca$^2+$
influx do not support the alternative hypothesis that this influx
of Ca$^2+$ is large enough to activate the myofilaments directly.
Yet the hypothesis of a CICR can be challenged because of many problems
and uncertainties related to the preparations and methods used for
skinned cardiac cell experiments.
- 15475522
- adenosine
- animals,
- caffeine,
- calcium,
- calmodulin,
- cell
- compartmentation,
- electron,
- feedback,
- gov't,
- guinea
- heart
- heart,
- liver,
- male,
- microscopy,
- myocardium,
- non-u.s.
- p.h.s.,
- permeability,
- phosphorylases,
- pigs,
- potassium,
- ranidae,
- research
- reticulum,
- saponins,
- sarcolemma,
- sarcoplasmic
- sodium,
- support,
- triphosphate,
- u.s.
- ventricles,
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