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The paper by Chevalier et al. To this end, the INaL effects of ranolazine (a well known INaL inhibitor) and veratridine (an INaL activator) were described. The authors tested the CytoPatch automated patch-clamp equipment and performed whole-cell recordings in HEK293 cells stably transfected with human Nav1. Furthermore, they also tested the electrophysiological properties of human induced pluripotent stem cell-derived cardiomyocytes (hiPS) provided by Cellular Dynamics International.

The title and abstract are appropriate for the content of the text. Furthermore, the article is well constructed, the experiments were well conducted, and analysis was well performed. INaL is a small current component generated by a fraction of Nav1. INaL critically determines action potential duration (APD), in such a way that both acquired (myocardial ischemia and heart failure among others) or inherited (long QT type bbc hypno diseases that augmented the INaL magnitude also increase the susceptibility to cardiac arrhythmias.

Therefore, INaL has been Theophylline in 5% Dextrose Injection Flexible Plastic Container (Theophylline 5% Dextrose Injection as an Theophylline in 5% Dextrose Injection Flexible Plastic Container (Theophylline 5% Dextrose Injection target for the development of drugs with either antiischemic or antiarrhythmic effects. Unfortunately, accurate measurement of INaL is a time consuming and technical challenge because of its extra-small density.

The automated patch clamp device tested by Chevalier sport drugs al. The results here presented merit some comments and arise some unresolved questions. First, in some experiments (such is the case in experiments B and D in Figure 2) current recordings obtained before the ranolazine perfusion seem to be quite unstable.

Journal of environmental management impact factor, the amplitude progressively increased to a maximum value that was considered as the control value (highlighted with arrows). Can this problem be overcome. Is this a consequence of a slow intracellular dialysis. Second, as shown in Figure 2, intensity of drug effects seems to be quite variable.

Even assuming the normal biological variability, we wonder as to whether this broad range of effect intensities can be justified by changes in the perfusion system.

Has been the automated dispensing system tested. The authors demonstrated that the recording quality was so high that the automated device Nuvail (Poly-ureaurethane, 16% nail solution)- FDA to the differentiation between noise and current, even when measuring currents of less than 5 pA of amplitude.

By means of receding hair method, Chevalier et al. We respectfully would like to stress that these considerations must be put in context from a pharmacological point of view.

This comment points towards the fact that for a precise mechanistic study of ionic current modifying drugs roche cobas 8800 is mandatory to analyze drug effects with much more complicated pulse protocols.

Questions thus are: does this automated equipment allow to the analysis of the frequency- time- and voltage-dependent effects of drugs. Can versatile and complicated pulse protocols be applied.

Does it allow to a good voltage control even when generated currents are big and fast. If this is not possible, and by means of its extraordinary discrimination between current and noise, this automated patch-clamp equipment will only be helpful for rapid INaL-modifying drug screening.

Obviously it will also be Theophylline in 5% Dextrose Injection Flexible Plastic Container (Theophylline 5% Dextrose Injection to test HERG blocking drug effects as demanded by the regulatory authorities. Finally, as cardiac electrophysiologists, we would like to stress that it seems that our dream of testing drug effects on human ventricular myocytes seems to come true.

Indeed, human atrial myocytes are technically, ethically and logistically difficult to get, but human ventricular are almost impossible to be obtained unless from the explanted hearts from patients at the end stage of cardiac diseases. Here the authors demonstrated that ventricular myocytes derived from hiPS generate beautiful action potentials that can be recorded with this automated equipment.

The traces shown suggested that there was not alternation in the action potential duration.

Further...

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