Differential Expression of hERG1 Channel Isoforms Reproduces Properties of Native IKr and Modulates Cardiac Action Potential Characteristics

can be reproduced by differential expression of ERG1a and ERG1b isoforms. Furthermore, the functional consequences of differential expression of ERG1 isoforms were explored as a potential mechanism underlying native heterogeneity of action potential duration (APD) and restitution. can be reproduced in heterologous expression systems by differential expression of ERG1a and ERG1b isoforms. Characterization of the macroscopic kinetics of ERG1 currents demonstrated that these were dependent on the relative abundance of ERG1a and ERG1b. Furthermore, we used a computational model of the ventricular cardiomyocyte to show that both APD and the slope of the restitution curve may be modulated by varying the relative abundance of ERG1a and ERG1b. As the relative abundance of ERG1b was increased, APD was gradually shortened and the slope of the restitution curve was decreased.. Importantly, our results suggest that regional differences in the relative abundance of ERG1 isoforms may represent a potential mechanism underlying the heterogeneity of both APD and APD restitution observed in mammalian hearts

Handlingsplansamtaler-en hån mod de arbejdsløse eller konstruktivt samspil med systemet?

Individuelle planer om aktivering og social integration er af voksende samfundsmæssig betydning. Handlingsplansamtaler og andre møder i den offentlige sektors frontlinie er komplekse og flertydige fænomener, som kun i ringe omfang er udforsket. Sprog, magt og professionelle vejledningsmetoder spiller afgørende ind på mødernes forløb. Spørgsmålet er blandt andet, om aktiveringspolitikken tager højde for de forudsætninger, som frontliniemedarbejdere og arbejdsløse repræsenterer

Tissue-specific effects of acetylcholine in the canine heart

Acetylcholine (ACh) release from the vagus nerve slows heart rate and atrioventricular conduction. ACh stimulates a variety of receptors and channels, including an inward rectifying current [ACh-dependent K(+) current (I(K,ACh))]. The effect of ACh in the ventricle is still debated. We compared the effect of ACh on action potentials in canine atria, Purkinje, and ventricular tissue as well as on ionic currents in isolated cells. Action potentials were recorded from ventricular slices, Purkinje fibers, and arterially perfused atrial preparations. Whole cell currents were recorded under voltage-clamp conditions, and unloaded cell shortening was determined on isolated cells. The effect of ACh (1–10 μM) as well as ACh plus tertiapin, an I(K,ACh)-specific toxin, was tested. In atrial tissue, ACh hyperpolarized the membrane potential and shortened the action potential duration (APD). In Purkinje and ventricular tissues, no significant effect of ACh was observed. Addition of ACh to atrial cells activated a large inward rectifying current (from −3.5 ± 0.7 to −23.7 ± 4.7 pA/pF) that was abolished by tertiapin. This current was not observed in other cell types. A small inhibition of Ca(2+) current (I(Ca)) was observed in the atria, endocardium, and epicardium after ACh. I(Ca) inhibition increased at faster pacing rates. At a basic cycle length of 400 ms, ACh (1 μM) reduced I(Ca) to 68% of control. In conclusion, I(K,ACh) is highly expressed in atria and is negligible/absent in Purkinje, endocardial, and epicardial cells. In all cardiac tissues, ACh caused rate-dependent inhibition of I(Ca.