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PMID: 7683508 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Molecular biology of the cell ·Vol. 4 ·No. 3 ·1993-03-00 ·Pages 347-52

Bezprozvanny IB, Ondrias K, Kaftan E, Stoyanovsky DA, Ehrlich BE

Abstract

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.

MeSH Terms
Animals Calcium/metabolism Calcium Channels/drug effects,metabolism Heparin/pharmacology In Vitro Techniques Inositol 1,4,5-Trisphosphate/metabolism Ion Channel Gating Muscle Proteins/drug effects,metabolism Pentosan Sulfuric Polyester/pharmacology Rabbits Ryanodine Receptor Calcium Release Channel Sarcoplasmic Reticulum/drug effects,metabolism
Chemicals
Calcium Channels Muscle Proteins Ryanodine Receptor Calcium Release Channel Pentosan Sulfuric Polyester Inositol 1,4,5-Trisphosphate Heparin Calcium
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Bezprozvanny I B
Department of Medicine, University of Connecticut Health Center, Farmington 06030.
Ondrias K
Kaftan E
Stoyanovsky D A
Ehrlich B E
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.4.3.347
Published
1993-03-00
Pages
347-52
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC300932
Subset
IM
Grants
NIGMS NIH HHS · GM-39029 · United States
NHLBI NIH HHS · HL-33026 · United States
External Links
PubMed source DOI: 10.1091/mbc.4.3.347 PMC Full Text View journal details
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