ABSTRACT: Key points The shape of the cardiac atrial action potential is influenced by the flow of a transient outward K(+) current (I(TO)) across atrial muscle cell membranes. Whether changes in I(TO) could alter atrial cell action potentials in ways that could affect mechanisms of abnormal heart rhythms (arrhythmias) is unclear, because currently available I(TO) blocking drugs are non-selective. We used the 'dynamic-clamp' technique, for the first time in atrial cells isolated from patients, and from rabbits, to electrically simulate selective changes in I(TO) during action potential recording. We found that I(TO) decrease prolonged atrial cell action potential duration and, under β-adrenergic-stimulation, provoked abnormal membrane potential oscillations (afterdepolarisations) that were preventable by I(TO) increase or a β-blocker. These results help us better understand the contribution of I(TO) to atrial cell action potential shape and mechanisms of arrhythmia, with potential implications for both the development and treatment of atrial fibrillation.
The Journal of Physiology 06/2012; 590(Pt 17):4289-305. · 4.72 Impact Factor