Summary of symbols
| Symbol | Definition |
| QEFF(V) | Effective equilibrium constant corresponding to movement of the S1–S4 voltage sensors (Fig. 1, C and E) |
| L | Equilibrium constant representing the subsequent (“late”) concerted opening of the S6 intracellular gate (Fig. 1, C and E) |
| a | S6 mutations act by multiplying L by this scaling factor |
| ΔGCO,WT | Energy required to activate the native (wild-type) channel (Eq. 1) |
| ΔΔGa | Additional energy needed to activate a mutant versus native channel (Eq. 1) |
| ΔV1/2 | Change in voltage required for half-maximal opening of mutant versus native channels |
| J(Ca2+) | Effective equilibrium constant describing the Ca2+-mediated transition between active (top row) and inactive (bottom row) conformations in Fig. 1 (C and E); J(Ca2+) ≈ PO‑PEAK/Keff |
| Keff | A constant closely analogous to the effective Ca2+ dissociation constant for CDI, which has been experimentally estimated at a value far less than unity (Tadross et al., 2008) |
| PO-PEAK | Peak open probability shortly after membrane depolarization (Eq. 2) |
| PO-SS | Steady-state open probability after a prolonged depolarization; for cases 1 and 2, PO-SS = PO-PEAK · (1 − FCDI) (Eq. 3); for case 3, PO-SS = PO-PEAK · (1 − FCDI · CDImax) (Eq. 5) |
| CDI | CDI, defined as fraction of peak current lost at steady state; for cases 1 and 2, CDI = FCDI (Eq. 4); for case 3, CDI = FCDI · CDImax (Eq. 5) |
| FCDI | Fraction of inactivated channels at steady state (Eq. 4) |
| CDImax | Fractional change in open probability of the normal mode versus the inactivated mode (Eq. 5) |
| VDI50, VDI300 | Experimental measure of VDI after 50 and 300 ms of depolarization (see Fig. 2 A and Materials and methods) |
| CDI50, CDI300 | Experimental measure of CDI after 50 and 300 ms of depolarization (see Fig. 2 A and Materials and methods) |
| Symbol | Definition |
| QEFF(V) | Effective equilibrium constant corresponding to movement of the S1–S4 voltage sensors (Fig. 1, C and E) |
| L | Equilibrium constant representing the subsequent (“late”) concerted opening of the S6 intracellular gate (Fig. 1, C and E) |
| a | S6 mutations act by multiplying L by this scaling factor |
| ΔGCO,WT | Energy required to activate the native (wild-type) channel (Eq. 1) |
| ΔΔGa | Additional energy needed to activate a mutant versus native channel (Eq. 1) |
| ΔV1/2 | Change in voltage required for half-maximal opening of mutant versus native channels |
| J(Ca2+) | Effective equilibrium constant describing the Ca2+-mediated transition between active (top row) and inactive (bottom row) conformations in Fig. 1 (C and E); J(Ca2+) ≈ PO‑PEAK/Keff |
| Keff | A constant closely analogous to the effective Ca2+ dissociation constant for CDI, which has been experimentally estimated at a value far less than unity (Tadross et al., 2008) |
| PO-PEAK | Peak open probability shortly after membrane depolarization (Eq. 2) |
| PO-SS | Steady-state open probability after a prolonged depolarization; for cases 1 and 2, PO-SS = PO-PEAK · (1 − FCDI) (Eq. 3); for case 3, PO-SS = PO-PEAK · (1 − FCDI · CDImax) (Eq. 5) |
| CDI | CDI, defined as fraction of peak current lost at steady state; for cases 1 and 2, CDI = FCDI (Eq. 4); for case 3, CDI = FCDI · CDImax (Eq. 5) |
| FCDI | Fraction of inactivated channels at steady state (Eq. 4) |
| CDImax | Fractional change in open probability of the normal mode versus the inactivated mode (Eq. 5) |
| VDI50, VDI300 | Experimental measure of VDI after 50 and 300 ms of depolarization (see Fig. 2 A and Materials and methods) |
| CDI50, CDI300 | Experimental measure of CDI after 50 and 300 ms of depolarization (see Fig. 2 A and Materials and methods) |