Voltage-dependent properties of three different gating modes in single cardiac Na+ channels

Three different modes of Na+ channel action, the F mode (fast inactivating), the S mode (slowly inactivating), and the P mode (persistent), were studied at different potentials in exceptionally small cell-attached patches containing one and only one channel. Switching between the modes was independent of voltage. In the F mode, the mean open time (tau o) at -30 and -40 mV was 0.14 and 0.16 ms, respectively, which was significantly larger than at -60 and 0 mV, where the values were 0.07 and 0.08 ms, respectively. The time before which half of the first channel openings occurred (t 0.5), decreased from 0.58 ms at -60 mV to 0.14 ms at 0 mV. The fit of steady-state activation with a Boltzmann function yielded a half-maximum value (V 0.5) at -48.1 mV and a slope (k) of 5.6 mV. The mean open time in the S mode increased steadily from 0.12 ms at -80 mV to 1.09 ms at -30 mV, but was not prolonged further at -20 mV (1.07 ms). Concomitantly, t 0.5 decreased from 1.61 ms at -80 mV to 0.22 ms at -20mV. Here the midpoint of steady-state activation was found at -61.2 mV, and the slope was 8.7 mV. The mean open time in the P mode increased from 0.07 ms at -60 mV to 0.45 ms at 0 mV and t 0.5 declined from 2.14 ms at -60 mV to 0.19 ms at +20 mV. Steady-state activation had its midpoint at -14.7 mV, and the slope was 10.9 mV. It is concluded that a single Na+ channel may switch among the F, S, and P mode and that the three modes differ by a characteristic pattern of voltage dependence of tau 0, t 0.5, and steady-state activation.