Effects of lidocaine on sarcolemmal fluidity and cellular cAMP in rat cardiomyocytes

Antiarrhythmic drugs with local anesthetic properties modify the physical state of membrane phospholipids and could change adenylate cyclase activity and, thus, influence cardiac ischemic arrhythmias. Adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in cardiomyocytes cultured from newborn rat and fluorescence anisotropy of sarcolemma-enriched membranes were investigated in the presence of a neutral anesthetic drug benzyl alcohol and of a cationic anesthetic drug lidocaine. Benzyl alcohol increased in a dose-dependent manner both sarcolemma fluidity and isoproterenol- or cholera toxin-stimulated cAMP accumulation. In contrast, benzyl alcohol inhibited cAMP accumulation in forskolin-stimulated cells. Lidocaine induced a dose-related inhibition of isoproterenol-, forskolin-, and cholera toxin-stimulated cAMP accumulation without eliciting any change in sarcolemma fluidity. The inhibitory effect of lidocaine on isoproterenol-stimulated cAMP accumulation was reversed when cells were pretreated with pertussis toxin. These data suggest that the inhibitory effect of lidocaine on cAMP synthesis might involve a polar interaction with the Gi regulatory subunit of adenylate cyclase. Such an effect could contribute, in vivo, to both the antiarrhythmic and the negative inotropic effect of lidocaine.