Similarities in the Effects of DIDS, DBDS and Suramin on Cardiac Ryanodine Receptor Function

Similarities in the Effects of DIDS, DBDS and Suramin on Cardiac Ryanodine Receptor Function The mechanisms involved in 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS)- and 4,4′-dibenzamidostilbene-2,2′-disulfonic acid (DBDS)- modification of sheep cardiac ryanodine receptor (RyR) channel function have been investigated. DIDS (50–500 μm) exerts at least three effects on single channel function. With Ca2+ as the permeant ion, DIDS increases both channel open probability (P o ) and single channel conductance in a similar manner to the effects observed with suramin. Both effects occur immediately and are fully reversible. Similar effects were observed with DBDS (10 μm–2 mm), a compound with the 4,4′-NCS groups of DIDS replaced with NHCOC6H5. DIDS (500 μm) also caused irreversible modification to the fully open channel level in 74% of the channels. This effect was not observed with suramin or DBDS (10 μm-1 mm). Competition studies with DBDS and suramin coupled with the close similarities in the effects of DIDS, DBDS and suramin on gating and conduction suggest that these ligands may all bind to the same sites on RyR. The DIDS-induced irreversible modification to the fully open state may result from the binding of the isothiocyanate groups to positively charged amino acids at or near the suramin binding sites although it is possible that this modification is unrelated to its other effects on channel function. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Similarities in the Effects of DIDS, DBDS and Suramin on Cardiac Ryanodine Receptor Function

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Publisher
Springer-Verlag
Copyright
Copyright © Inc. by 1999 Springer-Verlag New York
Subject
Life Sciences; Biochemistry, general; Human Physiology
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s002329900506
Publisher site
See Article on Publisher Site

Abstract

The mechanisms involved in 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS)- and 4,4′-dibenzamidostilbene-2,2′-disulfonic acid (DBDS)- modification of sheep cardiac ryanodine receptor (RyR) channel function have been investigated. DIDS (50–500 μm) exerts at least three effects on single channel function. With Ca2+ as the permeant ion, DIDS increases both channel open probability (P o ) and single channel conductance in a similar manner to the effects observed with suramin. Both effects occur immediately and are fully reversible. Similar effects were observed with DBDS (10 μm–2 mm), a compound with the 4,4′-NCS groups of DIDS replaced with NHCOC6H5. DIDS (500 μm) also caused irreversible modification to the fully open channel level in 74% of the channels. This effect was not observed with suramin or DBDS (10 μm-1 mm). Competition studies with DBDS and suramin coupled with the close similarities in the effects of DIDS, DBDS and suramin on gating and conduction suggest that these ligands may all bind to the same sites on RyR. The DIDS-induced irreversible modification to the fully open state may result from the binding of the isothiocyanate groups to positively charged amino acids at or near the suramin binding sites although it is possible that this modification is unrelated to its other effects on channel function.

Journal

The Journal of Membrane BiologySpringer Journals

Published: Mar 15, 1999

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