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• W2155013682 abstract "This study examined the effects of quinidine, quinine, and the quaternary quinidine derivative, quinidinium, on the conductance and activity of purified cardiac sarcoplasmic reticulum calcium release channels/ryanodine receptors (RyR) incorporated into planar lipid bilayers. Quinidine (50-500 microM) reduced the single-channel open probability in a voltage- and concentration-dependent manner. Reduction of channel activity was evident only at positive holding potentials where current flow is from the cytoplasmic to luminal side of the channel and when the drug was present only on the cytoplasmic face of the channel. A more pronounced effect was the appearance of a subconductance state at positive potentials. Single channel recordings and dose-response experiments revealed that at least two quinidine molecules were involved in reduction of the RyR activity. The permanently charged quinidinium compound produced nearly identical effects as quinidine when present only on cytoplasmic side of the channel, suggesting the positive-charged form of quinidine is responsible for the effects on the channel. There was no stereospecificity in the effects of quinidine because the levoisomer, 100 microM quinine, produced a similar subconductance activity of the channel. Ryanodine modification of the channel prevented subconductance activity. These findings suggest that the quinidine-induced subconductance activity may be the result of a partial occlusion of the channel pore interfering with ion conduction. Modification of the channel by ryanodine alters quinidine binding to the channel through a conformational change in protein structure." @default.
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• W2155013682 date "2002-05-01" @default.
• W2155013682 modified "2023-09-25" @default.
• W2155013682 title "Subconductance Activity Induced by Quinidine and Quinidinium in Purified Cardiac Sarcoplasmic Reticulum Calcium Release Channels" @default.
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• W2155013682 doi "https://doi.org/10.1124/jpet.301.2.729" @default.
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