Paralysis of rat skeletal muscle equally affects contractile properties as does permanent denervation MARIO BUFFELLI, EFREM PASINO and ALBERTO CANGIANO Dipartimento di Scienze Neurologiche e della Visione, Sezione di Fisiologia Umana, University ofVerona,Strada Le Grazie 8, 37134 Verona, Italy Received 29 July 1996; revised 2 January 1997; accepted 14 February 1997 Summary The effects oflong lasting (4±5 weeks) nerve conduction block and denervation were compared by investigating contractile, morphologicaland histochemical properties ofslow (soleus)and fast(EDL) rat skeletalmuscles.The block was based on improved perfusion techniques of the sciatic nerve with a tetrodotoxin (TTX) solution delivered at doses adequate to obtain maximal effects in the muscles. The TTX-inactivated axons retained normal histologicaland physiologicalproperties such as the ability to evoke full contractile responses, to regenerate, and to completely reinnervate muscle. In spite of their intactinnervation or oftheir full reinnervation, the TTX-paralysed muscles underwent weight loss, ®bre atrophy and reduction in force output quantitatively indistinguishable from those following denervation. The same was true for all other contractile parameters tested, that is,twitch speed,twitch to tetanus ratio, post-tetanic potentiation, endurance, and ®bre type composition. The results indicate the fundamental role of activity as a regulatory signal for muscle contractile properties, while they do notsupportthe notion ofa participation of chemical, activity-independent factors in this regulation. Introduction Motoneurons exerta profound in¯uence on muscle contractile properties. Experiments ofcross reinner- vation (Buller et al., 1960;Close,1972) have shown a dependency of contractile speed on the type, slow or fast, of reinnervating motoneurons. In agreement with this evidence,muscle ®bres belonging to the same motor unit are homogeneous in type (Edstro Èm & Kugelberg,1968;Burke et al.,1971).Furthermore, muscle denervation is followed by marked atrophy and changes in contractile and biochemical proper- ties (Tower, 1939;Finol et al., 1981;Gundersen, 1985;Spector,1985;Hennig & Lùmo, 1987;Ausoni et al., 1990).This neural regulation is important, Westgaard & Lùmo, 1988)or of normal muscles through their nerves (Salmons & Vrbova Â,1969;Pette et al.,1973;Salmons & Sreter, 1976).The importance of activity has also long been known from muscle disuse experiments (Fischbach & Robbins, 1969; for a review,see Spector, 1985). Chemical in¯uences from the nerve have in addition been proposed to take partin the neural regulation of contractileproperties.Thus, it has been reported thatectopicreinnervation ofsoleus muscle with ``fast'' foreign axons induces locally fast type myosin,while slow myosin is retained in the rest of the myo®bre extension (Salviati et al., 1986). Another argument brought in favour of Journalof Muscle Research and Cell Motility 18,683±695 (1997)