‘Tuned-up’ fatty acids - cure for cardiac arrhythmia?

Rhythmic irregularities in the heart, or cardiac arrhythmia, is a disorder in the rhythm of the heart that makes it beat too slowly, too quickly, or irregularly. Currently over 200,000 Swedes live with some form of irregular heart rhythm. The medicines that exist can suppress the irregularities, but not correct the fault. A collaborative project between labs in Linköping and Miami – and collaboration partners in Denmark and Finland – may be on the track of a future medicine, however. This is shown by the researchers in an article in the latest edition of the highly-ranked scientific journal PNAS.

Ion channels play a crucial role

Ion channels in the membranes of cardiac muscle cells play a crucial role in making the heart work as it should; malfunctioning ion channels are a common cause of arrhythmia. The researchers have been studying one of the heart’s most important ion channels: the IKs channel, made by the Kv7.1 ion channel and its auxiliary subunit KCNE1.

“The aim was to investigate whether polyunsaturated fatty acids can act as an anti-arrhythmic by affecting the IKs channel. It seems as if we have achieved our aim,” says Sara Liin, postdoc at Linköping University.

The group have shown how polyunsaturated fatty acids can open the Kv7.1 ion channel, which is important for the heart. The researchers already knew that polyunsaturated fatty acids could be beneficial in certain areas, for example in treating epilepsy. In these cases the patients were able to supply themselves with polyunsaturated fatty acids via their diet. But the polyunsaturated fatty acids we take in – through fish, for example – are not expected to affect the IKs channel, thus not helping a person suffering from cardiac arrhythmia. This is due to the important ion channel auxiliary subunit KCNE1, which blocks the action of the polyunsaturated fatty acids on the channel.

Identified several variations

“We have ‘tuned up’ the fatty acids by modifying their chemical properties. The fatty acids then open the channel, even in the presence of KCNE1. Through this ‘tune-up’ we have identified several variations of fatty acids that aid either opening or closing the channel,” says Ms Liin.

Much of the study was carried out on heart cells in rats and on the whole hearts of guinea pigs, where the modified fatty acids completely removed the rhythmic irregularities.

The hope is that, in the future, modified fatty acids can be developed into medicine for cardiac arrhythmia.

In addition to Sara Liin the article was authored by Malin Silverå Ejneby, Johan E. Larsson, Frida Starck Härlin and Fredrik Elinder of Linköping University.

Article in PNAS:
Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac IKs channel