The action of local anesthetics on myelin structure and nerve conduction in toad sciatic nerve.
X-ray scattering and electrophysiological experiments were performed on toad sciatic nerves in the presence of local anesthetics. In vitro experiments were performed on dissected nerves superfused with Ringer's solutions containing procaine, lidocaine, tetracaine, or dibucaine. In vivo experiments were performed on nerves dissected from animals anesthesized by targeted injections of tetracaine-containing solutions. In all cases the anesthetics were found to have the same effects on the x-ray scattering spectra: the intensity ratio of the even-order to the odd-order reflections increases and the lattice parameter increases. These changes are reversible upon removal of the anesthetic. The magnitude of the structural changes varies with the duration of the superfusion and with the nature and concentration of the anesthetic molecule. A striking quantitative correlation was observed between the structural effects and the potency of the anesthetic. Electron density profiles, which hardly showed any structural alteration of the unit membrane, clearly indicated that the anesthetics have the effect of moving the pairs of membranes apart by increasing the thickness of the cytoplasmic space. Electrophysiological measurements performed on the very samples used in the x-ray scattering experiments showed that the amplitude of the compound action potential is affected earlier than the structure of myelin (as revealed by the x-ray scattering experiments), whereas conduction velocity closely follows the structural alterations.
Mateu
L
L
Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela. Imateu@cbb.ivic.ve
Morán
O
O
Padrón
R
R
Borgo
M
M
Vonasek
E
E
Márquez
G
G
Luzzati
V
V
D000200:Action Potentials / Q000187:drug effects; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D002024:Bufo marinus; D018360:Crystallography, X-Ray; D003992:Dibucaine / Q000494:pharmacology; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D015394:Molecular Structure; D009186:Myelin Sheath / Q000737:chemistry / Q000187:drug effects*; D009431:Neural Conduction / Q000187:drug effects*; D011343:Procaine / Q000494:pharmacology; D012542:Scattering, Radiation; D012584:Sciatic Nerve / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D013748:Tetracaine / Q000494:pharmacology; D014965:X-Rays
D000779:Anesthetics, Local; D013748:Tetracaine; D011343:Procaine; D008012:Lidocaine; D003992:Dibucaine