IMPROVED GUINEA-PIG VENTRICULAR CELL MODEL INCORPORATING A DIADIC SPACE, I-KR AND I-KS, AND LENGTH-DEPENDENT AND TENSION-DEPENDENT PROCESSES

The guinea-pig ventricular cell model, originally developed by Noble e t al in 1991, has been greatly extended to include accumulation and de pletion of calcium in a diadic space between the sarcolemma and the sa rcoplasmic reticulum where, according to contempory understanding, the majority of calcium-induced calcium release is triggered. The calcium in this space is also assumed to play the major role in calcium-induc ed inactivation of the calcium current. Delayed potassium current equa tions have been developed to include the rapid (I-Kr) and slow (I-Ks) components of the delayed rectifier current based on the data of of He ath and Terrar, along with data from Sanguinetti and Jurkiewicz. Lengt h- and tension-dependent changes in mechanical and electrophysiologica l processes have been incorporated as described recently by Kohl et al . Drug receptor interactions have started to be developed, using the s odium channel as the first target. The new model has been tested again st experimental data an action potential clamp, and on force-interval and duration-interval relations; it has been found to reliably reprodu ce experimental observations.