CHANGES IN MYOSIN MESSENGER-RNA AND PROTEIN EXPRESSION IN DENERVATED RAT SOLEUS AND TIBIALIS ANTERIOR

Denervation differs from other models of reduced neuromuscular activat ion due to the absence of a nerve-muscle connection and limited data e xists regarding the effects of denervation on myosin heavy chain (MHC) expression. Thus, adult MHC expression (I, IIa, IIx, IIb) was studied in the rat soleus and tibialis anterior (TA) at the mRNA and protein levels 2, 4, 7, 10, 14, and 30 days following sciatic nerve transectio n. MHC protein content was quantified with SDS/PAGE and mRNA levels wi th the RNase-protection assay. Control soleus consisted predominately of type I MHC mRNA and protein, however. 4 days after denervation type I MHC mRNA was significantly decreased to 41 +/- 8% of control and co ntinued to remain below control values. Soleus IIa mRNA was significan tly elevated 7 and 10 days after denervation while IIx mRNA remained r elatively constant until 30 days when it increased to 197 +/- 23% of c ontrol. At the protein level, soleus I MHC significantly decreased to 80% of the total while IIa MHC significantly increased to 20% of the t otal. At 30 days, IIx MHC protein accounted for 9.4 +/- 1.6% of the to tal soleus MHC protein. In the TA, IIb mRNA was significantly decrease d to 57% of control by day 4 and remained significantly decreased for up to a month. TA IIx mRNA was also significantly decreased at 10 and 30 days after denervation. Similar to the soleus, TA IIa mRNA was sign ificantly increased over control 7-14 days after denervation. There we re no significant changes in TA MHC protein profile during one month o f denervation. In both the soleus and TA, denervation significantly sh ifted the MHC mRNA profile as early as 4 days following denervation wi thout any corresponding changes at the protein level. Significant mRNA changes without large changes in MHC protein composition continued th rough out the denervation period suggesting that the muscle may be pre vented from premature functional transitions by mechanisms such as dec reased mRNA stability, translational block, or increased turnover of n ewly synthesized proteins.