The energy regulating upstream kinase complex LKB1/MO25/STRAD is a potential novel regulator of thin filament function (1081.3)

AMP-activated protein kinase( AMPK) is a cellular energetic regulator that is known to modify both metabolic and contractile function in the heart. Phosphorylation by an upstream kinase complex (LKB1/MO25/STRAD; LMS) is required for AMPKactivation. Yet, the relationship between the LMS, AMPKactivation, and myofilamentfunction is unknown. Accordingly, we hypothesized that the upstream kinase complex can regulate myofilamentfunction independently or in combination with AMPK. To do this, demembranated (skinned) rat cardiac trabeculae were incubated with either the LMS or with varying ratios of the LMS with AMPKand myofilamentfunction was measured. Skinned rat trabeculae treated with the LMS alone were desensitized to Ca2+ and had lowered maximum tension. Adding increasing amounts of AMPKin combination with LMS reversed this effect increasing Ca2+-sensitivity of tension and maximum tension. We furthered hypothesized that the mechanism underlying this relationship is mediated through direct interaction ...