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

Kirstine Calloe, Eyal Nof, Thomas Jespersen, José M. Di Diego, Natalie Chlus, SØren Peter Olesen, Charles Antzelevitch, Jonathan M. Cordeiro

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1057-1066
Number of pages10
JournalJournal of Cardiovascular Electrophysiology
Volume22
Issue number9
DOIs
StatePublished - Sep 2011
Externally publishedYes

Keywords

  • atria
  • NS5806
  • sodium current
  • transient outward potassium current
  • ventricle

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