Order-disorder phenomena in myelinated nerve sheaths. IV. The disordering effects of high levels of local anaesthetics on rat sciatic and optic nerves.
Sequences of 15 minute X-ray scattering spectra were recorded with rat sciatic and optic nerves, superfused with tetracaine-containing Ringer solutions. The spectra were analysed using the algorithm advocated in this series of papers. The main results, as a function of the time of exposure to tetracaine, were: the mean value of the repeat distance increases; its variance decreases; the average number of membrane pairs per coherent domain decreases; the fraction of isolated membrane pairs increases. Eventually, the spectra were observed to give way to the continuous intensity curve of a single, isolated membrane pair. At all stages of the experiment the continuous intensity curves were found to differ from one type of nerve to the other, and to be invariant, for each type of nerve, with respect to the tetracaine treatment. The X-ray scattering study clearly identified the nature of the structural differences between the two types of myelin sheaths: in that of native sciatic nerves, packing disorder preferentially affects the cytoplasmic space of the membrane pair, and tetracaine disrupts the packing in that space; in the myelin of optic nerves it is the external space that is preferentially affected by packing disorder and disrupted by tetracaine. The time-course of the structure parameters showed that, at any stage of the experiment, tetracaine acts preferentially on the more highly disordered regions of the structure and totally disrupts them. These results corroborate earlier conclusions reported in the previous papers of this series. An electron microscope study was also performed on tetracaine-treated nerves: the results, in close agreement with those of the X-ray scattering study, neatly confirm the conclusions given above. In a more general way, the remarkable agreement between the results of the analysis of the X-ray scattering spectra and the electron microscope observations strongly supports the validity of the physical model used in this series of papers and the correctness of the mathematical treatment that we advocate. Finally, the relations between this work and the work of others are discussed. It must be stressed that the present work bears on the toxic rather than on the anaesthetic effects of tetracaine.
Mateu
L
L
Centro de Biofísica y Bioquímica IVIC, Caracas, Venezuela.
Luzzati
V
V
Villegas
G M
GM
Borgo
M
M
Vargas
R
R
D000200:Action Potentials / Q000187:drug effects; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D005990:Glycerol / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000187:drug effects* / Q000648:ultrastructure; D009900:Optic Nerve / Q000187:drug effects / Q000648:ultrastructure; D011343:Procaine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012542:Scattering, Radiation; D012584:Sciatic Nerve / Q000187:drug effects / Q000648:ultrastructure; D013748:Tetracaine / Q000494:pharmacology; D013997:Time Factors; D014965:X-Rays
D000779:Anesthetics, Local; D013748:Tetracaine; D011343:Procaine; D008012:Lidocaine; D005990:Glycerol