INACTIVATION OF SINGLE CARDIAC NA+ CHANNELS IN 3 DIFFERENT GATING MODES

In small cell-attached patches containing one and only one Na+ channel , inactivation was studied in three different gating modes, namely, th e fast-inactivating F mode and the more slowly inactivating S mode and P mode with similar inactivation kinetics. In each of these modes, en semble-averaged currents could be fitted with a Hodgkin-Huxley-type mo del with a single exponential for inactivation (tau(h).) tau(h) declin ed from 1.0 ms at -60 mV to 0.1 ms at 0 mV in the F mode, from 4.6 ms at -40 mV to 1.1 ms at 0 mV in the S mode, and from 4.5 ms at -40 mV t o 0.8 ms at +20 mV in the P mode, respectively. The probability of non -empty traces (net), the mean number of openings per non-empty trace ( op/tr), and the mean open probability per trace (p(open)) were evaluat ed at 4-ms test pulses. net inclined from 30% at -60 mV to 63% at 0 mV in the F mode, from 4% at -90 mV to 90% at 0 mV in the S mode; and fr om 2% at -60 mV to 79% at +20 mV in the P mode. op/tr declined from 1. 4 at -60 mV to 1.1 at 0 mV in the F mode, from 4.0 at -60 mV to 1.2 at 0 mV in the S mode, and from 2.9 at -40 mV to 1.6 at +20 mV in the P mode. p(open) was bell-shaped with a maximum of 5% at -30 mV in the F mode, 48% at -50 mV in the S mode, and 16% at 0 mV in the P mode. It i s concluded that 1) a switch between F and S modes may reflect a funct ional change of inactivation, 2) a switch between S and P modes may re flect a functional change of activation, 3) tau(h) is mainly determine d by the latency until the first channel opening in the F mode and by the number of reopenings in the S and P modes, 4) at least in the S an d P modes, inactivation is independent of pore opening, and 5) in the S mode, mainly open channels inactivate, and in the P mode, mainly clo sed channels inactivate.