Modelling and kinetic analysis on changrolin block of cardiac Na+ channels

Modelling and kinetic analysis on changrolin (CRL) blockade of cardiac Na+ channels based on the model of gate-related receptor hypothesis were performed by using computer simulation. A simple procedure suitable for analyzing steady-state blocking data was developed and used in the present studies. CRL blocks activated Na+ channels, and with the onset rate of 0.0347 AP-1 at driving rate of 1.0 Hz. The time constant of recovery from block at resting potential of -81 mV was 43.29 s, and increased with hyperpolarization, which suggested that CRL might be trapped in channel by activation gate. The studies also showed no shift on the h infinity curve in the presence of CRL. All these studies lead us to suggest that the binding site of CRL in Na+ channel is activation gate-related receptor site.