BisG10, a K⁺ channel blocker, affects the calcium release channel from skeletal muscle sarcoplasmic reticulum

Abstract

The action of bisGl0, a potent K* channel inhibitor, was tested on the Ca-" release from isolated sarcoplasmic reticulum vesicles of rabbit skeletal muscle. Using a rapid filtration technique, we found ,hat the drug inhibited Ca2*-induced Ca'-* release elicited in the presence of extravesieular K* as counter-ion. This inhibition was not reversed by the addition of valinomycin and still occurred when CI-was used as co-ion, indicating that not o;at;r' K" channels are involved in the inhibiting ¢fl'ect. We found that bisGl0 decreased the binding of ryanodine to sarcoplasmic reticulum vesicles, showinl3 that bisGl0 is able to block the sarcoplasmic reticulum Ca -'~ release channel.

Sarcoplasmic Reticulum K+ (TRIC) Channel Does Not Carry Essential Countercurrent during Ca2+ Release

“…BisG-10 is another higher affinity organic SR K þ channel blocker (43). BisG-10 blocks monovalent cation flux from SR vesicles (43), slows SR Ca 2þ release from skinned skeletal muscle fibers (44), and decreases ryanodine binding in skeletal muscle (45). In our hands, BisG-10 blocked single SR K þ and RyR2 channels almost equally well (see Fig.…”

What we don't know about the structure of ryanodine receptor calcium release channels

“…Another difference between the channels is that the RyR is thought to be a ‘single ion’ channel (the pore occupied by one ion at any time) and shows no saturation (up to 1 mol/L K + ), which is in contrast with the K + channels, which are ‘multi ion’ channels with clear saturation at high salt concentration. The K + and RyR channels share some pharmacological similarities that are consistent with the channels having a similar pore structure 44 . Three‐dimensional models of the RyR and IP 3 R pore based on KcsA structure can, in fact, account for the differences between the channels 45 …”

“…The K + and RyR channels share some pharmacological similarities that are consistent with the channels having a similar pore structure. 44 Three-dimensional models of the RyR and IP3R pore based on KcsA structure can, in fact, account for the differences between the channels. 45…”

Structure-Function Relation of Phospholamban: Modulation of Channel Activity as a Potential Regulator of SERCA Activity

“…The latter has been shown to increase the Ca 2+ content in the SR probably by corrupting the charge balance system [34]. The Ca 2+ content in the SR may also be increased because an inhibition of a K + conductance in the SR can inhibit the release Ca 2+ from the organelle [35].…”