Аннотация
Na$^+$/Ca$^2+$ exchange activity was studied in transfected
Chinese hamster ovary (CHO) cells expressing the wild-type cardiac
exchanger (NCX1.1) or mutants created by site-directed mutagenesis.
The activity of the wild-type exchanger, but not exchanger mutants
deficient in Ca$^2+$-dependent activation, was inhibited by sphingolipids
such as ceramide and sphingosine. We propose that sphingolipids interfere
with the regulatory activation of exchange activity by Ca$^2+$
and suggest that this interaction provides a means for monitoring
and regulating diastolic Ca$^2+$ levels in beating cardiac myocytes.
Exchange activity in CHO cells was also linked, through a poorly
understood feedback mechanism, to Ca$^2+$ accumulation within
internal stores such as the endoplasmic reticulum and the mitochondria.
Finally, the F-actin cytoskeleton was shown to modulate exchange
activity through interactions involving the exchanger's central hydrophilic
domain. We conclude that regulation of exchange activity in intact
cells involves multiple interactions with various lipid species,
cytosolic Ca$^2+$, organellar Ca$^2+$ stores, and the cytoskeleton.
- /&/
- analogs
- animals;
- axons,
- calcium
- calcium,
- cells;
- channels,
- cho
- contraction,
- cricetinae;
- cyclic,
- cytosol,
- decapodiformes;
- depsipeptides;
- derivatives/pharmacology;
- drug
- effects/physiology;
- exchanger,
- heart,
- metabolism/physiology;
- metabolism;
- mitochondria,
- mutagenesis,
- myocardial
- oxazoles,
- peptides,
- pharmacology;
- physiology;
- proteins,
- recombinant
- site-directed;
- sodium
- sodium,
- sodium-calcium
- sphingosine,
- transfection
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