title: Modification of the conductance and gating properties of ryanodine receptors by suramin.
abstract: Suramin, a polysulfonated napthylurea, increases the open probability and the single-channel conductance of rabbit skeletal and sheep cardiac ryanodine receptor channels. The main mechanism for the increase in Po is an increase in the duration of open lifetimes. The effects on conduction and gating are completely reversible and involve an interaction with the cytosolic side of the channel. 10 mM dithiothreitol had no effect on the suramin-induced increase in conductance or Po. Therefore oxidation of sulfhydryl groups on the channels does not appear to be involved. Suramin has been used as an antagonist of ATP at P2 purinoceptors, however, we find that suramin does not antagonize the effect of ATP at skeletal or cardiac ryanodine receptor channels. The unusual gating kinetics induced by suramin suggest that it does not interact with the adenine nucleotide binding site on the ryanodine receptor but rather binds at a novel site(s). The suramin-induced changes to channel gating and conduction do not prevent the characteristic modification of single-channel properties by micromolar ryanodine.
authors.affiliation: Cardiac Medicine, National Heart & Lung Institute, Imperial College, London.
authors.forename: R
authors.initials: R
authors.lastname: Sitsapesan
authors.forename: A J
authors.initials: AJ
authors.lastname: Williams
mesh_terms: D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D004553:Electric Conductivity; D006321:Heart / Q000187:drug effects*; D015640:Ion Channel Gating; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel; D012756:Sheep; D013498:Suramin / Q000494:pharmacology*
chemical_list: D015220:Calcium Channels; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D013498:Suramin; D002118:Calcium