VOLTAGE-DEPENDENT PROPERTIES OF 3 DIFFERENT GATING MODES IN SINGLE CARDIAC NA+ CHANNELS

Three different modes of Na+ channel action, the F mode (fast-inactiva ting), the S mode (slowly inactivating), and the P mode (persistent), were studied at different potentials in exceptionally small cell-attac hed 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 see -30 and -40 mV was 0.14 and 0.16 ms, respectively, whic h 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 fir st 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 Boltzma nn function yielded a half-maximum value (V-0.5) at -48.1 mV and a slo pe (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 fur ther at -20 mV (1.07 ms). Concomitantly, t(0.5) decreased from 1.61 ms at -80 mV to 0.22 ms at -20 mV. Here the midpoint of steady-state act ivation was found at -61.2 mV, and the slope was 3.7 mV. The mean open time in the P mode increased from 0.07 ms at -60 mV to 0.45 ms at 0 m V and t(0.5) declined from 2.14 ms at -60 mV to 0.19 ms at +20 mV. Ste ady-state activation had its midpoint at -14.7 mV, and the slope was 1 0.9 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(o) t(0.5), and steady-state activ ation.