PKA inhibition with H-89 decreased the peak amplitude of the intracellular Ca2+ transient in all fibers, while it decreased the decay rate constant only in phospholamban-expressing fibers.
Phosphorylation status modulates Ca2+ release in both fast- and slow-twitch skeletal muscle fibers, but modulates Ca2+ removal only in the presence of phospholamban.
The effects of phosphorylation status on Ca2+ release and Ca2+ removal were studied in fast-twitch flexor digitorum brevis and slow-twitch soleus skeletal muscle fibers enzymatically isolated from wild-type and phospholamban knockout (PLBko) mice. In all fibers the adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) inhibitor H-89 decreased the peak amplitude of the intracellular Ca2+ concentration (Ca2+) transient for a single action potential, and the PKA activator dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) reversed this effect, indicating modulation of Ca2+ release by phosphorylation status in all fibers. H-89 decreased the decay rate constant of the Ca2+ transient and DBcAMP reversed this effect only in phospholamban-expressing fibers (wild-type soleus), indicating modulation of Ca2+ removal only in the presence of phospholamban. A high basal level of PKA phosphorylation in soleus fibers maintained under our control conditions was indicated by the lack of effect of direct application of DBcAMP on Ca2+ release or Ca2+ removal in wild-type or PLBko soleus fibers and was confirmed by analysis of phospholamban from wild-type soleus fibers.
Liu et al. (Mon,) conducted a other in Ca2+ handling in skeletal muscle. H-89 (PKA inhibitor) and DBcAMP (PKA activator) vs. Control conditions was evaluated on Peak amplitude of the intracellular Ca2+ concentration transient and decay rate constant. PKA inhibition with H-89 decreased the peak amplitude of the intracellular Ca2+ transient in all fibers, while it decreased the decay rate constant only in phospholamban-expressing fibers.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: