Impact of Dyskalaemia on Calcium Transients, Isometric Force and Excitability in isolated Right Ventricular Trabeculae

Abstract

Background: There is a high prevalence of in-hospital patients exhibit dyskalaemia. Hypokalaemia (<3.5 mM) and hyperkalaemia (>5.0 mM) alter cell electrophysiology and increase cardiac susceptibility to deadly arrhythmias. Over the past couple of decades, few studies have investigated cardiac responses to alterations in extracellular potassium concentration. Objectives: This body of work set out to investigate control and hypertensive trabeculae responses to hypokalaemia and hyperkalaemia. Methods: The first study isolated right ventricular trabeculae (n = 17) from normotensive male Wistar rats (~350 g). In the second study, referred to as the hypertensive study, male Wistar rats (285 – 315g) were injected with 60 mg kg-1 of monocrotaline (MCT, n = 6) to induce pulmonary artery hypertension or sterile saline (control, n = 5); the right ventricular trabeculae were isolated four-weeks post injection. Both studies measured Ca²⁺ transient, isometric stress and stimulus voltage threshold responses to hypokalaemia (2.5 mM [K⁺]₀) and hyperkalaemia (6 mM - 25 mM [K⁺]₀), compared to normokalaemia (4 mM [K⁺]₀), and in the presence of isoproterenol (0.1 μM). Results: The key findings from this study are: 1. Hyperkalaemia at 15 mM [K⁺]₀ or more significantly increased stimulus voltage threshold. 2. Hypokalaemia or hyperkalaemia did not alter Ca²⁺ transient or isometric stress. 3. Isoproterenol did not modify Ca²⁺ transient and isometric stress responses to altered [K⁺]₀. 4. Hypokalaemia and hyperkalaemia exposure increased arrhythmia prevalence. 5. No alteration in trabeculae response to hypokalaemia and hyperkalaemia from hypertensive trabeculae compared to control trabeculae. Conclusions: This study characterized Ca²⁺ transient, isometric stress and stimulus voltage threshold responses from normotensive and hypertensive trabeculae in response to hypokalaemia and hyperkalaemia. Further, arrhythmic activity observed in response to hypokalaemia and hyperkalaemia supports altered RMP and repolarization as an arrhythmogenic substrate; understanding of detailed molecular mechanisms may lead to development of anti-arrhythmic treatment and prevention therapies.