Previous work has shown that patients with lowered blood potassium levels – a condition known as hypokalemia – have a higher risk of irregular heart rhythm (arrhythmia). Hypokalemia has been specifically linked to atrial fibrillation; a common arrhythmia that is associated with increased risk of heart failure and stroke. However, the reason for this association has been unclear. In this article, we show that hypokalemia predisposes atrial muscle cells to electrical instability, which causes them to fibrillate. We show that two mechanisms can occur, depending on the presence or absence of membrane invaginations called t-tubules in these cells. Cells that contain t-tubules exhibit an overload of calcium during hypokalemia, while cells without t-tubules exhibit a different type of instability resulting from ion channels being improperly activated. Since t-tubule density varies across the atria, our findings suggest that there may be complex regional differences in arrhythmia generation during hypokalemia. Furthermore, the realization that atrial myocytes develop over-activity by mechanisms which are distinct from the ventricle suggests that ventricular and atrial fibrillation may be differentially targeted by tailored treatments. These findings support a growing appreciation of the role of potassium homeostasis in maintaining electrical stability of both the ventricles and atria.
Read the article in Circulation Research
Circulation Research. 2020;126:889–906. DOI: 10.1161/CIRCRESAHA.119.315641