Fig. 9.

Slow inactivation is impaired in T704M cells. Changes in peak sodium current for representative WT (A) and T704M (B) cells in response to changes in the holding potential. Cells were allowed to stabilize for 20 min at −80 mV before beginning the test protocol. The protocol involved holding the cell at a specific potential for 5 min, while once every 15 sec the membrane potential was stepped to −100 mV for 30 msec and then to 0 mV for 20 msec. The peak current elicited by the test pulse to 0 mV is plotted. C, The steady-state slow inactivation curves for WT (filled circles,n = 8) and T704M (open circles,n = 7) cells are shown. D, Normalized Na current in representative WT (filled circles, n = 5) and T704M (open circles, n = 6) cells recovering from slow inactivation. The time axis is logarithmic. The recovery protocol required ∼45 min to complete and had two phases: short recovery times were obtained with individual recovery pulses, long recovery times were obtained in a continuous recording. E, Development of slow inactivation is shown to be slower for the T704M (open circles, n = 5) than for the WT channels (filled circles, n = 5). Cells were held at −100 mV for an increasing conditioning time. Details of the protocol are described in Materials and Methods.