Activation of the calcium release channel (ryanodine receptor) by heparin and other polyanions is calcium dependent

Heparin has been used as a potent competitive inhibitor of inositol 1,4,5-trisphosphate (IP3)-binding to IP3 receptors and to block IP3-gated calcium channels in bilayer experiments. In contrast to the effect on the IP3-gated channel, heparin (0.1-1 micrograms/ml) opened the Ca release channel (ryan...

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Bibliographic Details
Published in:Molecular biology of the cell 1993-03, Vol.4 (3), p.347-352
Main Authors: BEZPROZVANNY, I. B, ONDRIAS, K, KAFTAN, E, STOYANOVSKY, D. A, EHRLICH, B. E
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Calcium - metabolism
Calcium Channels - drug effects
Calcium Channels - metabolism
Cell physiology
Fundamental and applied biological sciences. Psychology
Heparin - pharmacology
In Vitro Techniques
Inositol 1,4,5-Trisphosphate - metabolism
Ion Channel Gating
Membrane and intracellular transports
Molecular and cellular biology
Muscle Proteins - drug effects
Muscle Proteins - metabolism
Pentosan Sulfuric Polyester - pharmacology
Rabbits
Ryanodine Receptor Calcium Release Channel
Sarcoplasmic Reticulum - drug effects
Sarcoplasmic Reticulum - metabolism
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Summary:Heparin has been used as a potent competitive inhibitor of inositol 1,4,5-trisphosphate (IP3)-binding to IP3 receptors and to block IP3-gated calcium channels in bilayer experiments. In contrast to the effect on the IP3-gated channel, heparin (0.1-1 micrograms/ml) opened the Ca release channel (ryanodine receptor). Other polyanions such as pentosan polysulfate and polyvinyl sulfate also activated the Ca release channel. The effect of polyanions on the Ca release channel was Ca dependent. Polyanion addition activated the Ca release channel when free Ca was > 80 nM, but was ineffective when free Ca was < 20 nM. The level of channel activation could be altered by manipulating the free Ca concentration. These results suggest that the polyanions act by increasing the local concentration of Ca near regulatory sites on the channel complex. As most cells have both types of intracellular channels, the opposite effects of the polyanions on the two channel types suggests that addition of polyanions to intact cells may produce multiple effects.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.4.3.347