Article Figures & Data
Figures
- Figure 1.
The I848T and L858H mutations of hNav1.7 alter activation and deactivation. A, Current traces recorded from representative HEK293 cells expressing either wild-type hNav1.7 or mutant channels, I848T or L858H. Cells were held at -100 mV, and currents were elicited with 50 msec test pulses to potentials ranging from -80 to 40 mV. B, Normalized peak current-voltage relationship for wild-type (filled squares; n = 29), I848T (open circles; n = 27), and L858H (open triangles; n = 27) channels. C, Representative tail currents of WT, I848T, and L858H channels. Cells were held at -100 mV and depolarized to -20 mV for 0.5 msec, followed by a repolarization to -50 mV to elicit tail currents. D, Time constants for tail current deactivation at repolarization potentials ranging from -40 to -100 mV for wild-type (filled squares; n = 7), I848T (open circles; n = 7), and L858H (open triangles; n = 7) hNav1.7 channels. Time constants were obtained with single exponential fits to the deactivation phase of the currents. Error bars represent SE.
- Figure 2.
The I848T and L858H mutations differentially alter inactivation of hNav1.7. A, Fast inactivation kinetics as a function of voltage for wild-type (filled squares; n = 8), I848T (open circles; n = 8), and L858H (open triangles; n = 8) hNav1.7 channels. Currents elicited as described in Figure 1 A were fit with Hodgkin-Huxley type m 3h model to estimate the inactivation time constants. B, Comparison of steady-state fast inactivation for wild-type (filled squares; n = 20), I848T (open circles; n = 19), and L858H (open triangles; n = 17) hNav1.7 channels. Currents were elicited with test pulses to 0 mV after 500 msec inactivating prepulses. C, Comparison of steady-state slow inactivation for wild-type hNav1.7 (filled squares; n = 9), I848T (open circles; n = 8), and L858H (open triangles; n = 9) hNav1.7 channels. Slow inactivation was induced with 30 sec prepulses, followed by 100 msec pulses to -120 mV to allow recovery from fast inactivation. A test pulse to 0 mV for 20 msec was used to determine the fraction of current available. Error bars represent SE.
- Figure 3.
The I848T and L858H mutations enhance ramp currents of hNav1.7. Representative ramp currents elicited with 500 msec ramp depolarizations from -100 to 0 mV from HEK293 cells expressing wild-type, I848T, and L858H channels.
