Figure 6. Voltage dependences of activation of I_NaR and I_NaP are indistinguishable.

(A) To test the hypothesis that non-inactivating voltage-gated sodium (Nav) channels underlie I_NaR, a depolarizing voltage ramp (blue) protocol (from –100 to 0 mV at 0.12 mV/ms) and a steady-state voltage step (green) protocol (with depolarizations from a holding potential of –100 mV to test potentials ranging from –75 to 10 mV in 5 mV increments) were used to reveal the magnitude and voltage-dependent properties of the non-inactivating (persistent) component of the Nav current, I_NaP. In addition, a hyperpolarizing voltage ramp (from 0 to –100 mV at 0.12 mV/ms or dV/dt) was used to reveal both I_NaR and I_NaP. Note that as I_NaR decays (see Figure 2B) during the hyperpolarizing voltage-ramp, the relative amplitudes of I_NaR and I_NaP vary during the ramp; the sum of the two current components, not the amplitudes of the individual components, therefore, are measured. The three representative records shown were obtained from the same Purkinje neuron. (B) The current-voltage relationships, derived from the records presented in (A) are plotted (in the corresponding color). From the records shown in the lowest panel of (A), the amplitudes of the steady-state inward currents at 25 ms at each test potential are plotted as points (green); the current amplitudes determined (at 2 ms intervals) from the ramp protocols (red and blue traces) are also plotted. As is evident, the current-voltage relations of the Nav currents recorded using the three different voltage-clamp protocols overlap; the magnitudes of the inward Nav currents are also indistinguishable. Similar results were obtained in four additional Purkinje neurons.