Abstract
Effect of NS5806 on Atrial Currents. 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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Cardiovascular Electrophysiology |
| Vol/bind | 22 |
| Udgave nummer | 9 |
| Sider (fra-til) | 1057-1066 |
| Antal sider | 10 |
| ISSN | 1045-3873 |
| DOI | |
| Status | Udgivet - sep. 2011 |