Inhibition by alcohols, halothane and chloroform of the Ca current in single frog ventricular cells

Changes in the Ca current, ICa, evoked by ethanol, long chain alcohols (hexanol, octanol and dodecanol) and two halogenated anesthetics (chloroform and halothane) were studied in single isolated frog ventricular cells using the whole cell patch clamp technique. Each of these general anesthetics induced a concentration-dependent decrease in ICa which was usually followed by a partial recovery during long application (5 min). However, an increase in ICa was observed with low ethanol concentrations. The potency of the alcohols was related to their oil-water partition coefficient in that the longer the carbon chain the greater the reduction in ICa. For example, to reduce ICa to half its control amplitude required 300 mM ethanol but only 0.3 microns dodecanol. The kinetics of ICa were also altered by exposure to the alcohols. The halogenated derivatives also decreased ICa and altered the kinetics of ICa, but in a different way to the alcohols. The complex and different alterations of ICa are probably the consequence of multifactorial effects induced by the general anesthetics. Previous suggestions have included alterations in the membrane lipid bilayer, membrane surface charge and hydrophobic pockets on channel proteins. We suggest that the increase in Cai may also participate to these effects.