The M1627K mutation increases the amplitude of currents elicited by slow ramp depolarizations. A, Representative ramp currents elicited by 600 ms long ramp depolarizations from -100 to +20 mV are shown recorded from a HEK293 cell expressing WT channels (black trace) and from one expressing M1627K channels (red trace). The peak transient current amplitude elicited in the WT cell was larger (3.4 nA) than that of the M1627K cell (2.8 nA). B, The average relative ramp current (ramp current divided by peak transient current amplitude) is larger for M1627K cells (red trace, n = 9) than for WT cells (black trace, n = 7). C, The properties of the averaged ramp currents are compared to the overlap between the voltage-dependence of activation (derived from the current-voltage relationship) and steady-state fast inactivation. The inverted amplitude of the WT ramp current was scaled so that it corresponded to the peak overlap between WT activation and steady-state fast inactivation (black shaded area). As can be seen, voltage-dependence of the WT ramp current corresponds to the region of overlap. Furthermore, the relative amplitude and voltage-dependence of the M1627K ramp currents corresponds to the overlap between M1627K activation and steady-state fast inactivation (red shaded area).
Dib-Hajj et al. Molecular Pain 2008 4:37 doi:10.1186/1744-8069-4-37