Na_v1.7 channel blocking activity of Smartox ProTx-II

ProTx-II is a potent blocker of Na_v1.7. The synthetic ProTx-II from Smartox demonstrates a similar biological activty than the natural version.

ProTx-II efficiently blocks the human Na_v1.7 channel. A, Families of transiently-expressed human Na_v1.7 current traces in control and in the presence of 1 nM ProTx-II. Currents were evoked by depolarizing pulses from -60 to 30 mV, while the cell was hold at -80 mV. B, Amplitude-voltage relationships obtained from A. C, Normalized conductance-voltage curves obtained from B showing the absence of shift in voltage-dependence. The curve was fitted by using a first-order Boltzmann relation. V_1/2 = -23.9 mV in control and -26.3 mV in the presence of 1 nM ProTx-II. Slope: 3.4 mV in control and 3.7 mV in the presence of ProTx-II. D, Representative recording traces of human Na_v1.7 current in the presence of 1 nM ProTx-II illustrating the kinetics of block onset (left panel). The current was elicited by a 50 ms-depolarizing pulse to -25 mV (estimated V_1/2) from a holding potential of -80 mV. Inter-sweep period was 10 sec. Current amplitudes were plotted against time (right panel). Black bar indicates toxin application. E, Dose-response Hill curve for ProTx-II block. The IC₅₀ value was 0.31 nM (n = 3 – 4 cells per concentration).