ACETYLCHOLINESTERASE ADAPTATION TO VOLUNTARY WHEEL RUNNING IS PROPORTIONAL TO THE VOLUME OF ACTIVITY IN FAST, BUT NOT SLOW, RAT HINDLIMB MUSCLES

Chronic enhancement of neuromuscular activity by forced exercise training programmes results in selective adaptation of the G(4) acetylcholinesterase (AChE) molecular form in hindlimb fast muscles of the rat, with only minor and non-selective AChE changes in the soleus. In order to shed further light on the physiological significance of this G(4) adaptation to training, we turned to a voluntary exercise model. The impact of 5 days and 4 weeks of voluntary wheel cage running on AChE molecular forms was examined in four hindlimb fast muscles and the slow-twitch soleus from two rat strains. Inbred Fisher and Sprague-Dawley rats, placed in live-in wheel cages, exercised spontaneously for distances which progressively increased up to an average of similar to 3 and 18 km/day, respectively, by the end of week 4. Fast muscles responded to this voluntary activity by massive G(4) increases (up to 420%) with almost no changes in A(12), so that by week 4 the tetramer became the main AChE component of these muscles. The additional G(4) was composed primarily of amphiphilic molecules, suggesting a membrane-bound state. The G(4) content of fast muscles was highly correlated with the distance covered by the rats during the 5 days before they were killed (r = 0.850-0.879, P < 0.001 in three muscles). The soleus muscle, in turn, responded to wheel cage activity by a marked selective reduction of its asymmetric forms-up to 45% for A(12). This A(12) decline, already maximal by day 5 of wheel cage running, showed no relationship with the distance covered. The present results constitute strong new evidence suggesting that the role of AChE in neuromuscular transmission is not limited solely to the rapid inactivation of just-released acetylcholine.