Background The tandem of P domains in a weak inward rectifying K+ channel (TWIK)‐related acid‐sensitive K + channel (TASK‐1; hK 2P 3.1) two‐pore–domain potassium channel was recently shown to regulate the atrial action potential duration. In the human heart, TASK ‐1 channels are specifically expressed in the atria. Furthermore, upregulation of atrial TASK ‐1 currents was described in patients suffering from atrial fibrillation ( AF ). We therefore hypothesized that TASK ‐1 channels represent an ideal target for antiarrhythmic therapy of AF . In the present study, we tested the antiarrhythmic effects of the high‐affinity TASK ‐1 inhibitor A293 on cardioversion in a porcine model of paroxysmal AF . Methods and Results Heterologously expressed human and porcine TASK ‐1 channels are blocked by A293 to a similar extent. Patch clamp measurements from isolated human and porcine atrial cardiomyocytes showed comparable TASK ‐1 currents. Computational modeling was used to investigate the conditions under which A293 would be antiarrhythmic. German landrace pigs underwent electrophysiological studies under general anesthesia. Paroxysmal AF was induced by right atrial burst stimulation. After induction of AF episodes, intravenous administration of A293 restored sinus rhythm within cardioversion times of 177±63 seconds. Intravenous administration of A293 resulted in significant prolongation of the atrial effective refractory period, measured at cycle lengths of 300, 400 and 500 ms, whereas the surface ECG parameters and the ventricular effective refractory period lengths remained unchanged. Conclusions Pharmacological inhibition of atrial TASK ‐1 currents exerts antiarrhythmic effects in vivo as well as in silico , resulting in acute cardioversion of paroxysmal AF . Taken together, these experiments indicate the therapeutic potential of A293 for AF treatment.
Here we present comparative studies of: (i) the formation of ZnO thin films via the sol-gel method using zinc acetate dihydrate (ZAD), 2-methoxyethanol (ME) as solvent, and the aminoalcohols (AA): ethanolamine, (S)-(+)-2-amino-1-propanol, (S)-(+)-2-amino-3-methyl-1-butanol, 2-aminophenol, and aminobenzyl alcohol, and (ii) elemental analyses, infrared spectroscopy, X-ray diffraction, scanning electron microscopy, absorption and emission spectra of films obtained after deposition by drop coating on glass surface, and thermal treatments at 300, 400, 500 and 600 °C. The results obtained provide conclusive evidences of the influence of the AA used (aliphatic vs. aromatic) on the ink stability (prior to deposition), and on the composition, structures, morphologies, and properties of films after calcination, in particular, those due to the different substituents, H, Me, or iPr, and to the presence or the absence of a –CH2 unit. Aliphatic films, more stable and purer than aromatic ones, contained the ZnO wurtzite form for all annealing temperatures, while the cubic sphalerite (zinc-blende) form was also detected after using aromatic AAs. Films having frayed fibers or quartered layers or uniform yarns evolved to “neuron-like” patterns. UV and photoluminescence studies revealed that these AAs also affect the optical band gap, the structural defects, and photo-optical properties of the films.
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