Electrical Muscle Activity Pattern and Transcriptional and Posttranscriptional Mechanisms Regulate PKA Subunit Expression in Rat Skeletal Muscle

摘要

We have examined protein kinase A (PKA) subunit expression in adult rat skeletal muscles. Northern blots identified PKA catalytic α and regulatory (R) I α and RII α subunits as the major subunits expressed in slowly contracting soleus (SOL) and rapidly contracting extensor digitorum longus (EDL) muscles. In addition, the steady-state RNA levels of PKA subunit mRNAs and activities of RI α and RII α promoters are similar in SOL and EDL. These data indicate that posttranscriptional mechanisms account for the two-fold differences in PKA subunit protein levels reported earlier. Electrical stimulation of denervated SOL with an EDL-like activity pattern (fast pattern) transformed SOL into an EDL-like muscle with regard to PKA protein levels. These experiments suggest that the posttranscriptional regulation is activity pattern-dependent. Denervation specifically increased RI α promoter activity and RI α mRNA levels in SOL and EDL. Further experiments indicated that the RI α 1a upstream sequences were activated following denervation. Direct electrical stimulation prevented the rise in RI α mRNA levels following denervation, demonstrating that electrical muscle activity regulates transcription.