The treatment of diseases of the musculoskeletal system can be optimised after researchers from Aarhus University have found a new correlation between a defective sodium–potassium pump and involuntary spasms, also called dystonia.

Researchers from Aarhus University have found a new cellular and very detailed correlation between a damaged sodium–potassium pump and a group of neurological diseases with symptoms of involuntary spasms and muscle contractions. A discovery that could have major significance for how we in future treat the movement disorder symptoms seen in a number of diseases connected to the central nervous system, including epilepsy and Parkinson's disease.

"The sodium–potassium pump is a critical enzyme that is found in each and every one of the body's cells. It continuously ensures the optimal ion balance. This leads to a build–up of considerable elector–chemical differences on the outside and inside of the cell. Differences that are important for our nerve cells electrical signals, for example," says one of the researchers behind the new findings, Associate Professor Karin Lykke–Hartmann from the Department of Biomedicine and Department of Clinical Medicine at Aarhus University.

Knowledge about the pump is therefore crucial for our understanding of important functions in the body and of the disease mechanisms which come into play when the pump does not function correctly. This knowledge is also important in order to develop new drugs targeted towards the correct cells in a faulty pump.

In order to investigate the phenomenon, the research group formed a mouse model with a disease mutation in the Atp1a3 gene, which encodes the mouse for a specific nerve cell isoform of the ion pump. Mutations in this gene are seen in a group of movement disorders in which the nerve cells that normally control our movements are affected.

"In the group of patients, we observe multiple overlapping symptoms such as dystonia, epilepsy, cognitive, defects and movement disorders. These types of diseases are in their very nature damaging and this is connected to the fact that non–functioning ion pumps are simply non–compatible with a good life," says Karin Lykke–Hartmann.

The results of the study were published in the journal PLOS Genetics.

The starting point for symptoms in patients with diseases related to mutations in the ATP1A3 gene is often stress. This can e.g. become apparent in the form of heat, exercise, bathing and sensory impressions, such as watching TV. These types of 'triggers' indicate that the fine–tuning of the ion pumps is strictly controlled.

"We saw that lower body temperatures gave spasms. We coupled this with some very specific nerve cells in the cerebellum, which have an irregular pattern during the spasm attacks," explains the researcher about the study, which itself is inspired by a biochemical research tradition based around the sodium–potassium pump at Aarhus University. It was here that Jens Chr. Skou discovered a disease mutation in the sodium–potassium pump in 1957, for which he received the Nobel Prize forty years later.

Partners: Researchers from Denmark and abroad. For example, Toke Jost Isaksen from Aarhus University, who is the primary author of the article, conducted trials during a PhD stay at Einstein College, NY, USA. The study is basic research. The study is supported by PUMPkin, the Graduate School of Health at Aarhus University, the Lundbeck Foundation, Th. Maigaards Eft., Fru Lily Benthine Lunds Foundation and the Foundation for the Promotion of the Health Sciences.

The article is titled, "Hypothermia–induced dystonia and abnormal cerebellar activity in a mouse model with a single disease–mutation in the sodium pump."