AJP - Heart and Circulatory Physiology, Vol 256, Issue 2 422-H427, Copyright © 1989 by American Physiological Society
Effects of lidocaine on sarcolemmal fluidity and cellular cAMP in rat cardiomyocytes
S. Roux, B. Escoubet, G. Friedlander, C. Le Grimellec, I. Bertrand and C. Amiel
U. 251, Departement de Physiologie, Faculte de Medecine X. Bichat, Universite Paris VII, France.
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.
