Defining determinant molecular properties for the blockade of the apamin-sensitive SKCa channel in guinea-pig hepatocytes: the influence of polarizability and molecular geometry.

QSAR studies of a series of blockers of the SK(Ca) channel in guinea-pig hepatocytes suggests that the polarizability of the blocker is an important factor controlling the binding to the channel. It is suggested that, upon binding, an ion-pair is formed, a process that is promoted by the reorganization of the water molecules. The polarizability is not adequate to describe the potency of the most potent blockers with a good stereochemical fit to the channel, presumably due to more specific interactions taking place.