The AMP-activated protein kinase (AMPK) is an aß? heterotrimer that is activated by low cellular energy status and affects a switch away from energy-requiring processes and toward catabolism . While it is primarily regulated by AMP and ATP, high muscle glycogen has also been shown to repress its activation  and . Mutations in the ?2 and ?3 subunit isoforms lead to arrhythmias associated with abnormal glycogen storage in human heart , ,  and  and elevated glycogen in pig muscle , respectively. A putative glycogen binding domain (GBD) has now been identified in the ß subunits. Coexpression of truncated ß subunits lacking the GBD with a and ? subunits yielded complexes that were active and normally regulated. However, coexpression of a and ? with full-length ß caused accumulation of AMPK in large cytoplasmic inclusions that could be counterstained with anti-glycogen or anti-glycogen synthase antibodies. These inclusions were not affected by mutations that increased or abolished the kinase activity and were not observed by using truncated ß subunits lacking the GBD. Our results suggest that the GBD binds glycogen and can lead to abnormal glycogen-containing inclusions when the kinase is overexpressed. These may be related to the abnormal glycogen storage bodies seen in heart disease patients with ?2 mutations.
- Cardiac arrhythmias
- Protein kinase