Comparison of the effects of a transient outward potassium channel activator on currents recorded from atrial and ventricular cardiomyocytes.
Publication/Presentation Date
9-1-2011
Abstract
INTRODUCTION: NS5806 activates the transient outward potassium current (I(to) ) in canine ventricular cells. We compared the effects of NS5806 on canine atrial versus ventricular tissues and myocytes.
METHODS AND RESULTS: NS5806 (10 μM) was evaluated in arterially perfused canine right atrial and right ventricular wedge preparations. In ventricular wedges NS5806 (10 μM) accentuated phase 1 in epicardium (Epi), with little effect in endocardium (Endo), resulting in augmented J-waves on the ECG. In contrast, application of NS5806 (10 μM) to atrial preparations had no effect on phase 1 repolarization but significantly decreased upstroke velocity (dV/dt) and depressed excitability, consistent with sodium channel block. Current and voltage-clamp recordings were made in the absence and presence of NS5806 in (10 μM) enzymatically dissociated atrial and ventricular myocytes. In ventricular myocytes, NS5806 increased I(to) magnitude by 80% and 16% in Epi and Endo, respectively (at +40 mV). In atrial myocytes, NS5806 increased peak I(to) by 25% and had no effect on the sustained current, I(Kur) . Under control conditions, I(Na) density in atrial myocytes was nearly double that in ventricular myocytes. NS5806 caused a shift in steady-state mid-inactivation (V(1/2)) from -73.9 ± 0.27 to -77.3 ± 0.21 mV in ventricular and from -82.6 ± 0.12 to -85.1 ± 0.11 mV in atrial cells, resulting in reduction of I(Na) in both cell types. Expression of mRNA encoding putative I(Na) and I(to) channel subunits was evaluated by qPCR.
CONCLUSION: NS5806 produces a prominent augmentation of I(to) with little effect on I(Na) in the ventricles, but a potent inhibition of I(Na) with little augmentation of I(to) in atria.
Volume
22
Issue
9
First Page
1057
Last Page
1066
ISSN
1540-8167
Published In/Presented At
Calloe, K., Nof, E., Jespersen, T., Di Diego, J. M., Chlus, N., Olesen, S. P., Antzelevitch, C., & Cordeiro, J. M. (2011). Comparison of the effects of a transient outward potassium channel activator on currents recorded from atrial and ventricular cardiomyocytes. Journal of cardiovascular electrophysiology, 22(9), 1057–1066. https://doi.org/10.1111/j.1540-8167.2011.02053.x
Disciplines
Medicine and Health Sciences
PubMedID
21457383
Department(s)
Fellows and Residents
Document Type
Article