A GitHub repository for the research project of analyzing K^+^ current recordings in mouse-model cardiomyocytes.
Potassium channels (Kv) are responsible for repolarizing the action potential in cardiomyocytes. There is a variety of Kv isoforms and corresponding currents (e.g., IKto, IKslow1, IKslow2) that contribute to different phases of repolarization. Because only the sum of their activities can be measured in the form of currents (IKsum), there is a need to decompose into individual K+ currents and their characteristics. Most existing studies separate and make inference of Kv activities via curve-fitting procedures, but there are limitations such that: 1) curve-fitting decomposition only relies on the shape of K+ current traces, which does not discern the underlying kinetics and interactions; 2) IKsum traces can only be fitted for one clamp voltage at each time, and estimated information is analyzed in a population-averaged way later. Here, we develop a novel concurrent data assimilation method that calibrates biophysics-based subject-specific computer models to decompose and delineate kinetics of Kv isoforms with multiple voltage-clamp responses simultaneously. The proposed method is evaluated and validated with whole-cell IKsum recordings from wild-type and chronically glycosylation-deficient cardiomyocytes. Experimental results show that the proposed method effectively handles multiple responses in the voltage-clamp protocol and describes the glycosylation-conferred perturbations observed experimentally to various Kv isoforms. In addition, we develop a graphical-user-interface (GUI) application that provides an enabling tool to biomedical scientists. The proposed method and pertinent software are shown to have strong potential to study Kv kinetics in various heart diseases.
We packaged the suggested method into a GUI application. Check KvApp_distribution folder and demo video.