Identified neurons in the buccal
ganglion of the marine mollusc Navanax inermis were used to examine the effects of
acetanilides on neuronal membrane properties.
Acetanilides increased the membrane potential and conductance of these neurons in a dose-dependent, reversible manner. These events would have the effect of decreasing membrane excitability.
Acetanilides increased the slope of the curve of membrane potential as a function of log [K+]o from 33 to 58 mV decade change in [k+]o and decreased the transient depolarization observed upon reducing [Cl]o. These results indicate that
acetanilides increase membrane potential and conductance by increasing the
potassium conductance of the membrane relative to the
chloride conductance. The variation in membrane potential as a function of external
alkali-
cation concentrations was used an as indirect measure of
alkali-
cation permeability.
Acetanilides altered the relative
cation permeability from Rb (1.25) greater than K (1.0) greater than Cs (0.60) greater than NaequalsLi (0.07) to K (1.0) greater than Rb (0.71) greater than Cs (0.31) greater than NaequalsLi (0.00). This shift in relative
cation permeability is interpreter, in terms of Eisenman's theory of membrane permselectivity, as indicating that
acetanilides increase the anionic field strength of the membrane. The ability of
acetanilides to increase membrane potential or alter permselectivity is directly correlated with octanol-water partition coefficient (r equals 0.96), indicating that hydrophobicity per se can account for almost all of the activity. Steric factors are unimportant. Analysis of published experiments on
acetanilide analgesia in mice reveals that hydrophobicity can also account for much of the activity in that system. Results obtained in the molluscan system may thus provide insight into the ionic, biophysical and physicochemical mechanisms underlying
acetanilide-induced
analgesia.