Abstract
Local anesthetics inhibit valinomycin-induced potassium uptake and basic protein-induced swelling of liver mitochondria. The present results suggest that a common feature of these effects of the local anesthetics on mitochondria is a stabilization of membrane structure. In view of the proposed role of protein conformational changes in nerve impulse conduction, the results suggest that the molecular mechanism of local anesthesia may involve an inhibition of membrane conformational changes rather than a direct inhibition of transport of monovalent or divalent cations, as generally believed. A correlation exists between the activity of these drugs on mitochondria and their activity on nerve conduction blockade. The mitochondrion may therefore serve as a useful model system to study local anesthetic action at the molecular level. Structure-activity studies indicate that the major determinant of potency of these anesthetics on mitochondria is the lipid solubility of the drug.
ACKNOWLEDGMENT We extend our appreciation to Dr. Jeanie M. Wood for carrying out several experiments and critically reviewing the manuscript.
- Copyright ©, 1973, by Academic Press, Inc.
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