Aim: 

Sera from post-streptococcal patients with movement disorders recognise piruvate kinase M1 (PK) in neurons. PK is known to alter the ATP levels in the cell microenvironment, regulating the ATP-sensitive potassium (K_ATP) channel activity in the heart. To explain the influences of the anti-neuronal PK antibody on neuronal cells, we explored the PK interaction with Kir6.2 and Kir6.1 subunits of K_ATP channel in brain cells.

Methods: 

Co-immunoprecipitation assays were used to analyze the Kir6.1- or Kir6.2-PK interaction in membrane fractions of the mouse brain. Co-localization in mouse brain cells of PK and Kir6.1 or Kir6.2 was analyzed by immunohistochemistry. The staining by two anti-PK-positive human sera and the putative co-localization with Kir6.1 or Kir6.2 proteins were also analyzed.

Results: 

PK was detected in Kir6.1 and Kir6.2 immunoprecipitates from mouse brain membranes, indicating that the protein is part of the K_ATP complex. In immunohistochemical experiments we have shown that PK is distributed in all brain regions and co-expressed with Kir6.1 or Kir6.2 in cerebral cortical neurons and in Purkinje neurons of the cerebellar cortex. Two PK-positive human sera stained cerebral cortical neurons and Purkinje cerebellar cells as does the anti-PK commercial antibody.

Conclusion: 

Our data suggest a probable interaction in neurons between the PK protein and the Kir6.2 and Kir6.1 subunits of the K_ATP channel. Our working hypothesis is that the anti-neuronal PK antibodies, by altering the metabolic pathway underlying the function of the K_ATP channel complex, perturb its physiology.