Details

Autor(en) / Beteiligte

• Trenor, Beatriz
• Cardona, Karen
• Romero, Lucia
• Gomez, Juan F.
• Saiz, Javier
• Rajamani, Sridharan
• Belardinelli, Luiz
• Giles, Wayne

Titel

Pro-arrhythmic effects of low plasma [K+] in human ventricle: An illustrated review

Ist Teil von

• Trends in cardiovascular medicine, 2018-05, Vol.28 (4), p.233-242

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• Potassium levels in the plasma, [K+]o, are regulated precisely under physiological conditions. However, increases (from approx. 4.5 to 8.0mM) can occur as a consequence of, e.g., endurance exercise, ischemic insult or kidney failure. This hyperkalemic modulation of ventricular electrophysiology has been studied extensively. Hypokalemia is also common. It can occur in response to diuretic therapy, following renal dialysis, or during recovery from endurance exercise. In the human ventricle, clinical hypokalemia (e.g., [K+]o levels of approx. 3.0mM) can cause marked changes in both the resting potential and the action potential waveform, and these may promote arrhythmias. Here, we provide essential background information concerning the main K+-sensitive ion channel mechanisms that act in concert to produce prominent short-term ventricular electrophysiological changes, and illustrate these by implementing recent mathematical models of the human ventricular action potential. Even small changes (~1mM) in [K+]o result in significant alterations in two different K+ currents, IK1 and HERG. These changes can markedly alter in resting membrane potential and/or action potential waveform in human ventricle. Specifically, a reduction in net outward transmembrane K+ currents (repolarization reserve) and an increased substrate input resistance contribute to electrophysiological instability during the plateau of the action potential and may promote pro-arrhythmic early after-depolarizations (EADs). Translational settings where these insights apply include: optimal diuretic therapy, and the interpretation of data from Phase II and III trials for anti-arrhythmic drug candidates.