CONDUCTION-BLOCKING CONCENTRATIONS OF ANESTHETICS INCREASE WITH NERVE AXON DIAMETER: STUDIES WITH ALCOHOL, LIDOCAINE AND TETRODOTOXIN ON SINGLE MYELINATED FIBERS’

Smirw.i, ALLAN AND PHILIP SEEMAN: Conduction-blocking concentrations of anesthetics increase with nerve axon diameter. studies with alcohol, lidocaine and tetrodotoxin on single myelinated fibers. J. Pharmacol. Exp. Ther. 201: 340-349, 1977. The equilibrium blocking conentrations of benzyl alcohol, lidocaine and tetrodotoxin just sufficient to block nerve impulse conduction were determined on myelinated single fibers of the bullfrog. For all three anesthetics it was found that the fastest conducting fibers (45 m/sec; about 18 diameter) required about 4 times higher blocking concentrations than the slowest fibers (8 m/sec; about 3 diameter). The drugs did not affect the frog sciatic nerve length constant (2 mm), using tetodotoxin to block the action potential. In agreement with Uehara’s single fiber study using urethane (Uehara, Y.: Jap. J. Physiol. 10: 267-274, 1960), it is concluded that smaller myelinated fibers are more sensitive to anesthetic blockade. The fact that different nerve fibers have dif-ferent sensitivities to the blocking actions of anesthetics has been known since 1905 (Dixon). Gasser and Erlanger (1929) first generalized the fact that smaller fibers were more suscepti-ble to anesthetics and De Jong and Wagman (1963) later proposed the explanation that smaller fibers had a higher surface/volume ra-tio, thus making them more vulnerable to the drugs. Received for publication September 17, 1976. ‘This work was supported by the Medical Re