[Hydrophobic interactions as the basis of the inotropic effect of verapamil]

The role of hydrophobic interactions (HI) of verapamil (V) in the mechanism of its blocking action on voltage-dependent Ca(2+)-channels was considered. For this purpose a comparative study of V inotropic effects and general anesthetics (GA) modeling V action on rhythmic switches of frog heart muscle was made. Concentration thresholds of the agents of inotropic action (Cth) were determined at two frequencies of stimulation, 4 and 30 switches per minute, resp. According to features of the inotropic action the studied agents were divided into two groups: Cth values of the former group were dependent on stimulation frequency (V, methanol, ethanol, isopropanol, chloral hydrate and acetone); Cth values of agents of the latter group were independent on stimulation frequency (n-butanol, n-pentanol, n-hexanol, and chloroform). In both groups Cth values were linearly dependent on agent hydrophobicities (in logarithmic scale). It indicates that HI play the main role in interaction of the studied agents with biostructures and primarily with protein structures of Ca(2+)-channels, which are targets for V-like ligand action. The results obtained make an experimental support of our earlier proposed "hydrophobic" model of blocking action of V on plasmalemmal L-type Ca(2+)-channels.