Interactions between intrinsic regulation and neural modulation of acetylcholinesterase in fast and slow skeletal muscles

Abstract

1. Initiation of subsynaptic sarcolemmal specialization and expression of different molecular forms of AChE were studied in fast extensor digitorum longus (EDL) and slow soleus (SOL) muscle of the rat under different experimental conditions in order to understand better the interplay of neural influences with intrinsic regulatory mechanisms of muscle cells. 2. Former junctional sarcolemma still accumulated AChE and continued to differentiate morphologically for at least 3 weeks after early postnatal denervation of EDL and SOL muscles. In noninnervated regenerating muscles, postsynaptic-like sarcolemmal specializations with AChE appeared (a) in the former junctional region, possibly induced by a substance in the former junctional basal lamina, and (b) in circumscribed areas along the whole length of myotubes. Therefore, the muscle cells seem to be able to produce a postsynaptic organization guiding substance, located in the basal lamina. The nerve may enhance the production or accumulation of this substance at the site of the future motor end plate. 3. Significant differences in the patterns of AChE molecular forms in EDL and SOL muscles arise between day 4 and day 10 after birth. The developmental process of downregulation of the asymmetric AChE forms, eliminating them extrajunctionally in the EDL, is less efficient in the SOL. The presence of these AChE forms in the extrajunctional regions of the SOL correlates with the ability to accumulate AChE in myotendinous junctions. The typical distribution of the asymmetric AChE forms in the EDL and SOL is maintained for at least 3 weeks after muscle denervation. 4. Different patterns of AChE molecular forms were observed in noninnervated EDL and SOL muscles regenerating in situ. In innervated regenerates, patterns of AChE molecular forms typical for mature muscles were instituted during the first week after reinnervation. 5. These results are consistent with the hypothesis that intrinsic differences between slow and fast muscle fibers, concerning the response of their AChE regulating mechanism to neural influences, may contribute to different AChE expression in fast and slow muscles, in addition to the influence of different stimulation patterns.

Influence of innervation on molecular forms of acetylcholinesterase in regenerating fast and slow skeletal muscles

“…Again, a similar phenomenon was observed during normal postnatal development in the rat (Sketelj et al, 1991). Taking into account its time course, a decrease of the 4 S AChE form may reflect a slow conversion of some myotubes, which are initially fast, into slow ones.…”

“…A similar mechanism is probably triggered during normal ontogenetic development of rat muscles causing restriction of the 16 S AChE form to the endplate region during the 4th week after birth (Sketelj and Brzin, 1980;Koenig and Rieger, 1981). However, the 16 S AChE form (A 12) predominated in SOL muscles of 2 week-old rats (Sketelj et al, 1991), whereas such an extreme increase of activity of this AChE form never occurs during SOL muscle regeneration. Similarity between innervated regenerating muscles and postnatal developing muscles is therefore only qualitative.…”

Termination and beyond: acetylcholinesterase as a modulator of synaptic transmission

“…AChE-S application to guinea pig hippocampal slices induced a long-term potentiation (LTP)-like effect in CA1 neurons, as indicated by increased EPSPs and increased population spikes evoked by stimulation of Schaffer collateral fibers (Appleyard 1995). The effects persisted after treatment with the cholinergic antagonists atropine and mecamylamine, suggesting that these modulatory effects are not mediated by Upregulation of AChE transcripts after 10 days in avian fast skeletal muscle Rimer and Randall 1999 Downregulation of AChE transcripts after 10 days in rodent fast and slow skeletal muscle Michel et al 1994 Decrease in AChE in spinal cord Tsim et al 1997 Preservation of the different AChE isoformal patterns in fast and slow muscles Sketelj et al 1991 Transient increase in G4 form (24-60 h) in fast muscles, and decrease in all other forms Gregory et al 1989;HodgesSavola and Fernandez 1991 Reduction in AChE activity in fast and slow muscles (14-42 days) and in NMJ Lomo et al 1985 Cross innervation of fast EDL muscle with slow SOL nerve and vice versa Replacement of each muscle characteristic isoformal pattern to that of the other muscle Dolenc et al 1994 Fast and slow electrical stimulation Induction of AChE pattern reminiscent of that of EDL in denervated SOL after fast stimulation. Preservation of SOL characteristic AChE pattern in denervated SOL after slow stimulation.…”

Reinnervation of a denervated slow muscle triggers high extrajunctional expression of the asymmetric molecular forms of acetyicholinesterase

“…However, no such reversion could be observed in the reinnervated fast EDL muscle. Reversion of AChE regulation in the SOL muscle lasted for about two to three weeks, which is comparable to about three weeks needed for downregulation of the extrajunctional A , , AChE synthesis observed during postnatal development or after muscle regeneration (Sketelj and Brzin, 1980;Sketelj et al, , erne et al, 1991. Since the A,, AChE down-regulation after reinnervation occurs in mature muscles, this process cannot be ascribed to muscle maturation itself but rather to some specific neural influence on muscle AChE regulation.…”