Gating current associated with inactivated states of the squid axon sodium channel

Sodium (Na) channel gating currents were measured in squid (Loligo forbesi) axons to study transitions among states occupied by the Na channel when it is inactivated. These measurements were made at high temporal resolution with a low-noise voltage clamp. The inactivation-resistant gating current, I_g,inact, could be separated into a very fast (τ = 5-25 μs) and a slower (τ = 40-200 μs) component over a wide range of test potentials (-140 mV to 80 mV) and for three different starting potentials (-70 mV, 0 mV, and 50 mV). The time constants for these components plotted against test potential lay on two bell-shaped curves; the time constants at any particular test potential did not depend on the starting potential. Both components had charge-voltage curves that saturated between -150 mV and 50 mV. A fast spike, similar to the fast component I_g,inact, was also apparent in recordings of the fully recovered total "on" gating current. I_g,inact (fast) and I_g,inact (slow) could not together be described by the simplest possible model, a linear three-state scheme; however, I_g,inact, (fast) could be modeled by a two-state scheme operating in parallel with other gating processes. I_g,inact (slow) and the gating current due to recovery from inactivated states into resting states could together be well described by a three-state scheme. This lends support to models in which a pair of inactivated states are connected by a single voltage-dependent step to the resting states of the Na system.