The asymmetric molecular forms of AChE and the expression of collagen Q in mature and immature fast and slow rat muscles

Abstract

There is a major difference between fast and slow rat muscles in regard to acetylcholinesterase (AChE) expression in their extrajunctional regions: the activity of the asymmetric forms of AChE (A 8 and A 12) is quite high extrajunctionally in slow muscles but virtually absent in fast muscles. The latter is due to the nearly complete suppression of the expression of AChE-associated collagen Q (ColQ) in the extrajunctional regions of fast muscle fibers, in contrast to its ample expression in slow muscles. This difference is partly caused by different neural activation patterns of fast vs. slow muscle fibers, which determine the levels of mRNA of ColQ. Whereas the changes of the levels of ColQ mRNA in slow muscles, observed in response to different electrical stimulation patterns, are completely reversible, the extrajunctional suppression of ColQ expression in fast muscle fibers seems to be irreversible in this respect. Calcineurin signaling pathway in slow muscle fibers, activated by high average sarcoplasmic calcium concentration resulting from tonic low-frequency muscle fiber activation pattern, maintains high mRNA levels of ColQ in the extrajunctional regions of the slow soleus muscles. A different, calcineurin-independent regulatory pathway is responsible for maintaining high ColQ expression in the neuromuscular junctions of fast muscle fibers. Immature rat muscle fibers, both fast and slow, however, display relatively high levels of the A forms of AChE and ColQ mRNA during the early postnatal period. Four days after birth, ColQ mRNA levels are already 2-fold higher in slow than in fast muscle fibers. Muscle regeneration after injury is a repetition of its ontogenetic development, originating from the muscle satellite cells. The extrajunctional levels of ColQ mRNA in non-innervated regenerating fast and slow muscles, however, are not significantly different, but they become about 2- to 3-fold higher in the regenerating soleus than in the fast STM already after several days of innervation by their respective nerves. We are currently testing a hypothesis that intrinsic differences exist between fast and slow muscle fibers in regard to their capacity to express ColQ extrajunctionally, and that these differences may originate in the stem cells of these muscle fibers.