V810M increases peak current, hyperpolarizes voltage-dependent
activation, and delays deactivation of Nav1.7. (a)
Representative whole-cell current traces from HEK293 cells transiently
transfected with WT (black) or V810M (red) channels. Cells were held at
–120 mV and stepped to potentials ranging from –80 to +40 mV in 5 mV
increments for 100 ms with 5 s between pulses. (b) Current density for
WT (black squares, n = 18) and V810M (red circles,
n = 16) channels showing a significant increase in
peak current density for V810M. Current density was calculated by
normalizing peak currents to cell capacitance. (c) Normalized peak
current-voltage relationship for activation of WT (black squares,
n = 18) and V810M (red circles,
n = 16) channels showing a significant hyperpolarized
shift in activation of V810M. (d) Voltage-dependent activation of WT
(black squares, n = 18) and V810M (red circles,
n = 16) channels showing a small but significant
hyperpolarized shift in activation of V810M. Conductance curves were
normalized to the maximum conductance value and fit to a Boltzmann
equation. (e) Deactivation time constants for WT (black squares,
n = 17) and V810M (red circles,
n = 11) channels showing significantly slowed kinetics
of deactivation for V810M over a voltage range of –65 to –40 mV. Data
are expressed as means ± SEM.