Summary
The first alteration noted after denervation of the extensor digitorum longus muscles of rats was a decrease in resting membrane potential (RMP) which occurred at about 2h. The exact time course of this membrane depolarization was dependent upon the intramuscular length of the degenerating nerve stump. The decrease in RMP occurred prior to any detectable alteration in adenosine triphosphate and phosphocreatine content of the muscle. Prior to failure of spontaneous transmitter release, which occurred 10 h after denervation, some muscle fibres showed an increase in frequency of the miniature end-plate potentials (m.e.p.p.) with no alterations in amplitude and shape of the single potentials. Appearance of areas sensitive to acetylcholine (ACh) on the extra-junctional membrane occurred at 24 h after crushing the motor nerve. At 48 h after denervation a high ACh-sensitivity appeared at the muscle-tendon region, but was not detected in the majority of the muscle fibres studied midway between end-plate region and muscle-tendon area. The transverse resistance of a unit area of the muscle membrane was increased 3 days after denervation.
These results provide evidence that the processes of post-denervation changes occur in the following temporal sequence: a) partial depolarization of the postsynaptic muscle membrane; b) a decrease and subsequent cessation of the spontaneous transmitter release preceded in some fibres by a transient increase in m.e.p.p. frequency; c) appearance of extrajunctional ACh sensitivity; d) increase in the transverse resistance of a unit area of the muscle membrane. It is suggested that the motor nerve releases more than one neurotrophic substance.
Zusammenfassung
Nach Denervation des M. extensor digitorum longus der Ratte nahm als zuerst bemerkbare Veränderung 2 Std später das Ruhemembranpotential (RMP) ab. Der genaue zeitliche Verlauf dieser Membrandepolarisation hing von der intramuskulären Länge des degenerierenden Nervenendes ab. Das RMP fiel früher ab als der Gehalt an ATP und P-Kreatin. Die spontane Transmitter-Freisetzung hörte 10 Std nach der Denervation auf; zuvor jedoch nahm in einigen Muskelfasern die Frequenz der Miniatur-Endplattenpotentiale (M.E.P.P.) zu; Amplitude und Form der einzelnen Potentiale waren dabei nicht verändert. Die erste Acetylcholin (ACh)-Empfindlichkeit außerhalb der motorischen Endplatte war 24 Std nach der Denervation festzustellen, nach 48 Std auch im Sehnen-Bereich. Die Mehrzahl der untersuchten Muskelfasern zeigte aber zu dieser Zeit noch keine ACh-Empfindlichkeit zwischen Endplatten- und Sehnen-Bereich. Die elektrischen Konstanten der Muskelmembran waren am 3. Tag nach Denervation erhöht.
Diese Ergebnisse machen es wahrscheinlich, daß die Veränderungen nach Denervation in folgender zeitlicher Reihenfolge auftreten: a) Partielle Depolarisation der postsynaptischen Muskelmembran; b) Verringerung und schließlich Sistieren der spontanen Transmitter-Freisetzung mit einem zuvor vorübergehenden Anstieg der M.E.P.P. Frequenz in einigen Muskelfasern; c) Auftreten von ACh-Empfindlichkeit außerhalb der motorischen Endplatte; d) Anstieg des Membranwiderstandes. Außerdem wird angenommen, daß der motirische Nerv mehr als eine neurotrophische Substanz freisetzt.
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This work was supported by grant from the National Institute of Health (NB-08223).
Recipient of a Buswell Fellowship from the State University of New York at Buffalo and on leave of absence from the Christian-Albrechts-Universität, Kiel, West Germany.
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Albuquerque, E.X., Schuh, F.T. & Kauffman, F.C. Early membrane depolarization of the fast mammalian muscle after denervation. Pflugers Arch. 328, 36–50 (1971). https://doi.org/10.1007/BF00587359
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DOI: https://doi.org/10.1007/BF00587359