Antiarrhythmic peptides: A new antiarrhythmic principle (part 15). DISCUSSION

Regarding the mechanism of action of AAP10, it was assumed that AAP10 increases cellular coupling because an enhancement of dispersion normally is ascribed to a reduction in cellular coupling and vice versa. The present study provides more evidence for this mechanism of action because it was possible to demonstrate a reduction in coupling time in…

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Antiarrhythmic peptides: A new antiarrhythmic principle (part 14). DISCUSSION

Antiarrhythmic peptides: A new antiarrhythmic principle

DISCUSSION Antiarrhythmic peptides were described for the first time in 1980 by Aonuma and colleagues . These peptides were found to enhance synchronization in embryonic chick heart cell aggregates and to suppress aconitine and CaCl2-induced arrhythmias in mice in vivo. However, the mechanism of action remained unclear. After Argentieri and coworkers reported that the natural…

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Antiarrhythmic peptides: A new antiarrhythmic principle (part 13). RESULTS

Antiarrhythmic peptides: A new antiarrhythmic principle

In additional experiments the spatial structure of AAP10 was clarified using Fourier transformation NMR spectra (1H-NMR, 13C-NMR in D2O or DMSO at 25°C and 40°C). With these investigations it was possible to define the peaks identifying carbon atoms in the molecule and the various hydrogens. A chemical shift was found of the OH moiety of…

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Antiarrhythmic peptides: A new antiarrhythmic principle (part 12). RESULTS

Antiarrhythmic peptides: A new antiarrhythmic principle

The SDS-PAGE containing connexin 43 is shown in Figure 5. There was a twofold increase in radioactivity compared with the supernatant, which was not different from background activity. In the next step of the further purification of the connexins, ie, of con-nexin 43, radioactivity was lost. Finally, connexin 43 was found, but no 14C-labelled AAP10…

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Antiarrhythmic peptides: A new antiarrhythmic principle (part 11). RESULTS

Antiarrhythmic peptides: A new antiarrhythmic principle

In additional experiments the influence of 1 |j,mol/L AAP10 on intracellular electrophysiology of guinea pig papillary muscles was investigated. No alteration in action potential duration was found at 90% repolarization (165±5 versus 164±6 ms), action potential duration at 20% repolarization (80±4 versus 78±8 ms), resting membrane potential (-84±1 versus -84±3 mV), overshoot potential (29±2 versus…

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Antiarrhythmic peptides: A new antiarrhythmic principle (part 10). RESULTS

Antiarrhythmic peptides: A new antiarrhythmic principle

RESULTS AAP10 and natural AAP reduced the dispersion of the epicardial ARIs, meaning that local differences in ARI duration were reduced by the peptide, as shown in Figure 1. It became obvious that with both peptides the percentage of ARI durations within the ±5 ms interval around the mean ARI was increased in a concentration-dependent…

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Antiarrhythmic peptides: A new antiarrhythmic principle (part 9). ANIMALS AND METHODS

Nuclear magnetic resonance spectra: For all nuclear magnetic resonance (NMR) spectra, common Fourier-transformed free induction decay NMR spectra were used. All NMR were registered in both D2O and DMSO in order to allow detection of OH moieties. Tetramethylsilan was used as an internal standard. First, 13C-NMR spectra were registered and the peaks were associated with…

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