Electrical muscle activity pattern and transcriptional and posttranscriptional mechanisms regulate PKA subunit expression in rat skeletal muscle.
We have examined protein kinase A (PKA) subunit expression in adult rat skeletal muscles. Northern blots identified PKA catalytic alpha and regulatory (R) I alpha and RII alpha 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 alpha and RII alpha promoters are similar in SOL and EDL. These data indicate that posttranscriptional mechanisms account for the twofold 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 alpha promoter activity and RI alpha mRNA levels in SOL and EDL. Further experiments indicated that the RI alpha 1a upstream sequences were activated following denervation. Direct electrical stimulation prevented the rise in RI alpha mRNA levels following denervation, demonstrating that electrical muscle activity regulates transcription.
Hoover
Frank
F
Department of Physiology, University of Oslo, Norway. frank.hoover@vir.uib.no
Kalhovde
John M
JM
Dahle
Maria Krudtaa
MK
Skålhegg
Bjørn
B
Taskén
Kjetil
K
Lømo
Terje
T
D024506:5' Flanking Region / Q000235:genetics; D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics*; D005091:Exons / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D017930:Genes, Reporter / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D018656:Muscle Fibers, Fast-Twitch / Q000166:cytology / Q000201:enzymology*; D018657:Muscle Fibers, Slow-Twitch / Q000166:cytology / Q000201:enzymology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology* / Q000294:innervation; D009469:Neuromuscular Junction / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics
D012333:RNA, Messenger; D017868:Cyclic AMP-Dependent Protein Kinases