Characterization of the Pharmacology of YM-198313 on Volume-Regulated Anion Channels

抄録

Activation of the volume-regulated anion channels (VRAC) is considered to be involved in arrhythmia, but it has not yet been fully elucidated because of the lack of its high affinitive and selective compounds. A newly synthesized compound, YM-198313 (sodium 4-({[2-(methylthio)benzyl]amino}-5-[(1-phenylethyl)thio]isothiazol-3-olate), strongly inhibited VRAC in HeLa cells with an IC₅₀ of 3.03±0.05 μM. However, YM-198313 weakly affected both the Ca²⁺-activated Cl⁻ channels in HTC cells and the cAMP-activated Cl⁻ channels in T84 cells, demonstrating that this compound is selective for VRAC among Cl⁻ channels. At 10 μM, YM-198313 almost completely (100±7.8%) inhibited the VRAC current in guinea pig atrial myocytes. However, at the same concentration, YM-198313 showed little inhibitory effect on the cardiac cation currents in ventricular myocytes. We believe that YM-198313 is a potent and selective VRAC inhibitor, therefore, it should be use to clarify the role VRAC plays in arrhythmia.