Effects of calcium on the local anesthetic suppression of ionic conductances in squid axon membranes
Narahashi, T.; Frazier, D.T.; Takeno, K.
Journal of Pharmacology and Experimental Therapeutics 197(2): 426-438
1976
ISSN/ISBN: 0022-3565 PMID: 5601 Document Number: 108780
The effects of varying the external Ca concentration on the suppression of membrane ionic conductances by procaine and benzocaine were examined under voltage-clamped conditions in axon membranes of the squid Loligo pealei. The suppression of peak conductance and steady-state conductance by procaine or benzocaine applied externally or internally was not affected by changing the external Ca concentration between 10 and 100 mM. When the Ca concentration was lowered below 10 mM (5 or 2 mM), the procaine effect was slightly potentiated. This augmentation could not be ascribed to an acceleration in the rate of penetration of procaine into the axon in low Ca solutions. The resting membrane conductance was slightly decreased by procaine in a manner independent of the external Ca concentration. The maximum effect of procaine on resting conductances was obtained at a concentration much lower than that required for maximum suppression of peak and steady-state conductances. The present results are not compatible with the hypothesis that Ca competes with local anesthetics for a negatively charged site on the membrane. It is suggested that hydrophobic interactions of local anesthetic molecules with the membrane affect the resting membrane conductance, whereas coulombic interactions are responsible for the conductance changes observed during nerve activity.