Slow‐to‐fast transformation of denervated soleus muscles by chronic high‐frequency stimulation in the rat.

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Abstract
1. Adult soleus muscles were denervated and stimulated directly for 2-130 days with ''fast'' (short pulse trains at 100 Hz) or ''slow'' (continuously at 10 Hz, or long pulse trains at 15 Hz) stimulus patterns. 2. At the end of the period of stimulation isometric twitches and tetani and isotonic shortening velocities were measured. Frozen cross-sections were later examined with antibodies against myosin heavy chains specific for adult fast, adult slow and fetal myosin. 3. Isometric twitch duration (twitch time-to-peak and half-relaxation time) decreased during intermittent 100 Hz stimulation to values that were almost as fast as in the normal extensor digitorum longus (EDL)(95 and 94% transformation). The major part of the decrease occurred between 2 and 21 days after the onset of stimulation, and was accompanied by post-tetanic potentiation of the twitch, ''sag'' in tension during an unfused tetanus, lower twitch/tetanus ratio and marked shifts to the right (higher frequencies) of the tension-frequency curve of the muscle. In contrast, during 10 or 15 Hz stimulation the isometric twitch duration remained slow, the twitch continued to show post-tetanic depression and absence of ''sag'', while the twitch/tetanus ratio increased. 4. Denervation per se led to a slight increase and, then, after about a month, to a moderate and gradual decrease in twitch duration. The twitch/tetanus ratio increased markedly and post-tetanic depression became less pronounced or disappeared. Muscle weight and particularly tetanic tension were markedly reduced and these reductions were to a large extent counteracted by electrical stimulation. 5. Implantation of sham electrodes had no effect on twitch duration of denervated or innervated control muscles, but reduced tetanic tension in the innervated control muscles. 6. Maximum isotonic shortening velocity of the whole muscle (mm/s) increased during intermittent 100 Hz stimulation to a value as fast as in the normal EDL (110% transformation). Since the muscle fibres also increased in length (35%) maximum intrinsic shortening velocity (fibre lengths/s) was only incompletely transformed (55%). The increase in Vmax occurred between 7 and 14 days after the onset of stimulation. 7. All the fibres stimulated intermittently at 100 Hz were strongly labelled with anti-fast myosin and more than 90% were in addition weakly labelled by anti-slow myosin. Weak and variable labelling with anti-fast myosin was first detected 7 days after the onset of stimulation. In contrast, essentially all the fibres stimulated at 10 or 15 Hz showed no binding of anti-fast but strong binding of anti-slow myosin. Denervation per se increased the fraction of fibres labelled by anti-fast myosin but even after 2 months more than half the fibres (57%) reacted only with anti-slow myosin. 8. From the beginning to the end of intermittent stimulation at 100 Hz the bulk of the muscle consisted of large fibres unreactive with anti-fetal myosin which stains regenerating fibres. This indicated that the slow-to-fast transformation occurred in pre-existing adult fibres and was not the result of muscle injury followed by formation of new fibres of a fast type.