Hypokalemia occurs in up to 20% of hospitalized patients and is associated with in-hospital mortality rates that are 10-fold higher than that of the entire hospitalized population. The increased mortality is linked to increased incidence of ventricular and atrial fibrillation. Understanding the proarrhythmic role of hypokalemia in these two conditions thus has important implications for preventative treatment in a large number of patients.
It has been unclear whether differing types of arrhythmia result from direct and perhaps distinct effects of hypokalemia. In a new publication from the Louch group at IEMR two distinct mechanisms is discovered, depending on the presence or absence of t-tubules; cell membrane invaginations important for regulating Ca2+ concentration in cardiomyocytes.
The t-tubule network is different in ventricular and atrial cells. In ventricular cells there is a dense and well-organized t-tubule network. In atrial cells t-tubule density varies, with epicardial cells as the most frequently tubulated.
Experiments that were performed showed that proarrhythmic currents were robustly induced in hypokalemic ventricular cells, and in the subpopulation of atrial cells that contained t-tubules. However, in atrial cardiomyocytes lacking t-tubules, hypokalemia triggered arrhythmia trough proarrhythmic Na+ currents, which was induced by ultra-rapid K+ currents and brief action potentials.
These findings suggests that there may be complex regional differences in arrhythmia generation during hypokalemia. The realization that untubulated atrial myocytes develop over-activity by a mechanism which is distinct from the tubulated ventricular myocytes suggests that ventricular and atrial fibrillation may be differentially targeted by treatment.
To read the full story check out the paper published in Circulation Research
Vol. 126, No. 7, 2020;126:889–906