The plateau outward current in canine ventricle, sensitive to 4‐aminopyridine, is a constitutive contributor to ventricular repolarization

• Published in: British journal of pharmacology 2007-11, Vol.152 (6), p.870-879
• Main Authors: Sridhar, A, Cunha, D N Q, Lacombe, V A, Zhou, Q, Fox, J J, Hamlin, R L, Carnes, C A
• Format: Article
• Language: English
• Subjects: 4-Aminopyridine - pharmacology; 4‐aminopyridine; action potential; Action Potentials - drug effects; Algorithms; Animals; canine; Computer Simulation; Delayed Rectifier Potassium Channels - drug effects; Delayed Rectifier Potassium Channels - physiology; Dogs; Dose-Response Relationship, Drug; Electrophysiology; Heart - drug effects; Heart Ventricles - drug effects; In Vitro Techniques; Markov Chains; Myocardium - cytology; Myocardium - metabolism; Myocytes, Cardiac - drug effects; Patch-Clamp Techniques; Potassium Channel Blockers - pharmacology; potassium current; Receptors, Adrenergic, beta - drug effects; Receptors, Adrenergic, beta - physiology; repolarization; Research Papers; Solutions; ventricle; ventricular myocyte
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0707403

Background and purpose: IKur (Ultra‐rapid delayed rectifier current) has μM sensitivity to 4‐aminopyridine (4‐AP) and is an important modulator of the plateau amplitude and action potential duration in canine atria. Kv1.5 encodes IKur and is present in both atria and ventricles in canines and humans. We hypothesized that a similar plateau outward current with μM sensitivity to 4‐AP is present in canine ventricle. Experimental approach: We used established voltage clamp protocols and used 4‐AP (50 and 100 μM) to measure a plateau outward current in normal canine myocytes isolated from the left ventricular mid‐myocardium. Key results: Action potential recordings in the presence of 4‐AP showed significant prolongation of action potential duration at 50 and 90% repolarization at 0.5 and 1 Hz (P