Resolving artefacts in voltage-clamp experiments with computational modelling: an application to fast sodium current recordings.

Cellular electrophysiology is the foundation of many fields, from basic science in neurology, cardiology, oncology to safety critical applications for drug safety testing, clinical phenotyping, etc. Patch-clamp voltage clamp is the gold standard technique for studying cellular electrophysiology. Yet, the quality of these experiments is not always transparent, which may lead to erroneous conclusions for studies and applications.

Recording ten-fold larger I conductances with automated patch clamping using equimolar Cs solutions.

The rapid delayed rectifier potassium current (I) is important for cardiac repolarization and is most often involved in drug-induced arrhythmias. However, accurately measuring this current can be challenging in human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes because of its small current density. Interestingly, the ion channel conducting I, hERG channel, is not only permeable to K ions but also to Cs ions when present in equimolar concentrations inside and outside of the cell.

The Utrecht University Honours Program review project: example based scientific publishing training aimed at bachelor medical students.

Introduction: Medical undergraduate students receive limited education on scholarly publishing. However, publishing experiences during this phase are known to influence study and career paths. The medical bachelor Honours Program (HP) at Utrecht University initiated a hands-on writing and publishing course, which resulted in nine reviews published in internationally peer reviewed academic journals.

Towards the Development of AgoKirs: New Pharmacological Activators to Study K2.x Channel and Target Cardiac Disease.

Inward rectifier potassium ion channels (I-channels) of the K2.x family are responsible for maintaining a stable negative resting membrane potential in excitable cells, but also play a role in processes of non-excitable tissues, such as bone development. I-channel loss-of-function, either congenital or acquired, has been associated with cardiac disease.

Drug-likeness of linear pentamidine analogues and their impact on the hERG K channel - correlation with structural features.

This work presents drug-likeness and the cardiotoxicity profiles of six potent pentamidine analogs 1-6 and three new compounds 7-9 as chemotherapeutics for therapy of pneumonia. A combination of experimental and computational approaches was used in the cardiotoxicity examination. The hERG trafficking and functionality of the hERG currents were tested by western blot analyses, immunofluorescent staining procedures, and patch-clamp electrophysiological assays.

Disease Associated Mutations in K Proteins Linked to Aberrant Inward Rectifier Channel Trafficking.

The ubiquitously expressed family of inward rectifier potassium (K) channels, encoded by genes, is primarily involved in cell excitability and potassium homeostasis. Channel mutations associate with a variety of severe human diseases and syndromes, affecting many organ systems including the central and peripheral neural system, heart, kidney, pancreas, and skeletal muscle. A number of mutations associate with altered ion channel expression at the plasma membrane, which might result from defective channel trafficking.