Comparison of the effects of a transient outward potassium channel activator on currents recorded from atrial and ventricular cardiomyocytes

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. (J Cardiovasc Electrophysiol, Vol. 22, pp. 1057‐1066, September 2011)