Abstract
Hypokalemia, an abnormally low level of potassium (K+), is a electrolyte imbalance that commonly occurs in heart failure patients. Hypokalemia is well known to induce lethal ventricular arrhythmia. However, the effects of hypokalemia in failing hearts that have undergone electrophysiological remodeling, i.e., the reactivation of fetal-type ion channels, remain unexplored. We have examined the effect of hypokalemia in the myocytes of transgenic mice overexpressing the hyperpolarization-activated, cyclic nucleotide-sensitive (HCN) channel in the heart (HCN2-Tg mice). Perfusion with a mild hypokalemic solution containing 3 mM K+ induced ectopic ventricular automaticity in 55.0% of HCN2-Tg mouse myocytes. In the remaining HCN2-Tg mouse myocytes, the resting membrane potential (RMP) was more depolarized than that of wild-type myocytes subjected to the same treatment and could also be hyperpolarized by an HCN channel blocker. We conclude that in hypokalemia in our mice model, the HCN2 channel was constitutively activated at the hyperpolarized RMP, thereby destabilizing the electrophysiological activity of ventricular myocytes.
Highlights
Hypokalemia, a type of pro-arrhythmic electrolyte disturbance characterized by an abnormally low level of potassium (K+), is frequently observed in patients with cardiovascular disease [1, 2]
This was presumably due to the voltage-gated K + channels comprising the “repolarization reserve” of murine myocytes being less sensitive to hypokalemia
We previously reported that the resting membrane potential (RMP) of HCN2-Tg mouse myocytes were not significantly different from those of WT mouse myocytes in normal Tyrode solution, but that they were depolarized by β-adrenergic stimulation, followed by the generation of SAPs [9]
Summary
Hypokalemia, a type of pro-arrhythmic electrolyte disturbance characterized by an abnormally low level of potassium (K+), is frequently observed in patients with cardiovascular disease [1, 2]. Heart failure patients in particular often receive diuretics, some of which can cause an increase in the elimination of K + in the urine, leading to hypokalemia. Almost 50% of heart failure patients die suddenly, most probably due to ventricular arrhythmia. It is important to control the serum potassium homeostasis. The mechanism of ventricular arrhythmia in heart failure is not fully understood. Electrophysiological remodeling, i.e., reactivation of fetal cardiac genes, including T-type Ca2+ channel and hyperpolarization-activated, cyclic nucleotide-sensitive (HCN) cation channels (HCN2 and -4) have been reported to increase the vulnerability to arrhythmia [6, 7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
