Alterations of K+ currents in isolated human ventricular myocytes from patients with terminal heart failure.

Abstract

Prolongation of the action potential has been postulated to be a major reason for the altered diastolic relaxation of the heart in patients with severe heart failure. To investigate the electrophysiological basis for this action potential prolongation in terminal heart failure, K' currents were recorded in single ventricular myocytes isolated from 16 explanted hearts of patients undergoing transplantation. Results from diseased hearts were compared with ventricular cells isolated from six undiseased donor hearts. Action potential duration was significantly prolonged in cells from patients with heart failure. A delayed rectifier K' current was hardly detectable in most cells, and if it could be recorded, it was very small in both diseased and undiseased cells. When currents were normalized for cell surface area, the average current density of the inward rectifier K' current was significantly reduced in diseased cells when compared with normal control cells (hyperpolarization at -100 mV, -15.9±2.2 vs -9.0±+1.2 pA/cm2; P<.01). In addition, a large transient outward K+ current could be recorded in human myocytes. The average current density of the time-dependent component of this transient outward K+ current was significantly reduced in heart failure (depolarization at +40 mV, 9.1+ 1.0 vs 5.8±0.64 pA/cm2; P<.01). Action potential prolongation in severe heart failure may partially be explained by a reduction in current densities of the inward rectifier K+ current and of the transient outward K+ current. These alterations may thereby have a significant effect on cardiac relaxation.

Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm

“…Our electrophysiological data support the possibility that similar alterations occur in the STZ‐hyperglycemic mouse model employed here. Importantly, reduction in the outward K + Kv currents and prolongation of AP duration in mammals appear to be a conserved response to a variety of physio‐ and pathological conditions dictated by an increase in workload of the myocardium, including ischemic cardiomyopathy,60, 61 hypertension,62 pressure overload,63 aging,20, 64 and heart failure 18, 65, 66. Thus, the enhanced beat‐to‐beat variability observed in diabetic myocytes may represent a feature shared with other diseased conditions.…”

Multiscale model of the human cardiovascular system: Description of heart failure and comparison of contractility indices

“…It has been shown that heart failure originates at the cellular scale [28,29,30]. Alterations in ionic currents and calcium handling lead to a prolonged action potential, a lower …”

The role of arrhythmias in the progression of heart failure

“…a'i the lQ~a.J:d t:.ec:tifut:. CJl..t:.-rent, X KI , and the transient outward current, ITO' [5,6]; as well as a decrease in Na/K pump current [7]. It should be pointed out that the clinical relevance of the prolongation of action potential duration is still uncertain, since it has been shown to be present mostly at long, and often unphysiologic, cycle lengths.…”