Functional, pharmacologic, and ultrastructural correlates in degenerating rat motor nerve terminals

Abstract

Functional, pharmacologic, and ultrastructural correlates during Wallerian degeneration were sought in rat phrenic nerve terminals. Functional and pharmacologic responses were studied in vitro in paired denervated and innervated hemidiaphragms 14 to 22 h after unilateral phrenicotomy. Following this, the diaphragms were fixed for electron microscopic examination of junctional regions. A progressive loss of neurally evoked and isometrically recorded twitch tension fully defined the course of transmission failure in the junctional population. This time course concurs with that reported by others. The twitch method, by measuring the population response, discloses that structurally altered nerve terminals, at 16 h after denervation, are able to transmit. Total transmission failure at 22 h correlates with the disappearance of the nerve terminal structure and its replacement by the Schwann cell. Using edrophonium to test motor nerve terminal function, via the production of twitch potentiation, showed that loss of this pharmacologic response during degeneration paralleled the single twitch loss. Edrophonium testing further disclosed a slowed development of twitch potentiation. This pharmacologic abnormality appeared at the onset of transmission loss and is seen to signal motor nerve terminal dysfunction. This abnormality is also associated with the earliest changes in nerve terminal ultrastructure.