Activation mechanism and novel binding sites of the BK channel activator CTIBD.

The large-conductance calcium-activated potassium (BK) channel, which is crucial for urinary bladder smooth muscle relaxation, is a potential target for overactive bladder treatment. Our prior work unveiled CTIBD as a promising BK channel activator, altering and This study investigates CTIBD's activation mechanism, revealing its independence from the Ca and membrane voltage sensing of the BK channel. Cryo-electron microscopy disclosed that two CTIBD molecules bind to hydrophobic regions on the extracellular side of the lipid bilayer.

Discovery and characterization of a potent activator of the BK channel that relives overactive bladder syndrome in rats.

The large-conductance Ca-activated K channel (BK channel) is involved in repolarizing the membrane potential and has a variety of cellular functions. The BK channel is highly expressed in bladder smooth muscle and mediates muscle relaxation. Compounds that activate the BK channel have therapeutic potential against pathological symptoms associated with the overactivity of bladder smooth muscle.

Identification and Characterization of a Novel Large-Conductance Calcium-Activated Potassium Channel Activator, CTIBD, and Its Relaxation Effect on Urinary Bladder Smooth Muscle.

The large-conductance calcium-activated potassium channel (BK channel) is expressed on various tissues and is involved in smooth muscle relaxation. The channel is highly expressed on urinary bladder smooth muscle cells and regulates the repolarization phase of the spontaneous action potentials that control muscle contraction. To discover novel chemical activators of the BK channel, we screened a chemical library containing 8364 chemical compounds using a cell-based fluorescence assay.