Three different gating models for inactivation of the Ito in ventricular myocytes of rats and mice

Kinetic models to describe the time course of the Ca(2+)-independent outward potassium current (Ito) in cardiac ventricular cells were constructed. The Ito traces were recorded from isolated myocytes of rats and mice using the whole-cell configuration of the patch-clamp technique. An iterative method was developed to eliminate the capacitive transient overlapping the early part of the Ito. The isolated Ito curves were then fitted by Hodgkin-Huxley type functions and different inactivation gating mechanisms were identified in various groups of the animals. In some Wistar rats a single inactivation route was found. Another group of Wistar rats and diabetic BB/Mol rats showed two independent inactivation pathways both of which resulted in a completely closed channel. In lean specimen of C-57 mice and in streptozotocin-treated Wistar rats the two inactivation gates gave closed channels only when both parallel inactivating transitions have been completed. In this case a possible interaction between the gating particles has been revealed.