Dynamic clamping human and rabbit atrial calcium current: narrowing ICaL window abolishes early afterdepolarizations

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp13564-list-0001">Early‐afterdepolarizations (EADs) are abnormal action potential oscillations and a known cause of cardiac arrhythmias. Ventricular EADs involve reactivation of a Ca²⁺ current (I CaL) in its ‘window region’ voltage range. However, electrical mechanisms of atrial EADs, a potential cause of atrial fibrillation, are poorly understood.Atrial cells were obtained from consenting patients undergoing heart surgery, as well as from rabbits. I CaL was blocked with nifedipine and then a hybrid patch clamp/mathematical‐modelling technique, ‘dynamic clamping’, was used to record action potentials at the same time as injecting an artificial, modifiable, I CaL (I CaL,D‐C).Progressively widening the I CaL,D‐C window region produced EADs of various types, dependent on window width. EAD production was strongest upon moving the activation (vs. inactivation) side of the window.EADs were then induced by a different method: increasing I CaL,D‐C amplitude and/or K⁺ channel‐blockade (4‐aminopyridine). Narrowing of the I CaL,D‐C window by ∼10 mV abolished these EADs.Atrial I CaL window narrowing is worthy of further testing as a potential anti‐atrial fibrillation drug mechanism.