Fig. 2.
QX-314 permeates through human (h) transient receptor potential vanilloid 1 (TRPV1) and human transient receptor potential cation channel, subfamily A, member 1 (TRPA1) channels to produce use-dependent block of sodium current. (A, B) Representative traces of sodium currents of Nav1.7 expressed in human embryonic kidney 293t (HEK-293t) lacking TRP channels. Currents were activated by 100 test pulses applied at 10 Hz in presence of 100 μM QX-314 in the extracellular solution (A) or the intracellular pipette solution (B). (C) Peak current amplitudes activated at 10 Hz were normalized to the amplitude of the first pulse and plotted against the pulse number. Note that although extracellular QX-314 at both 100 μM and 5 mM did not induce use-dependent block, 100 μM QX-314 in the pipette solution induced a strong use-dependent block. (D, F) Normalized peak current amplitudes activated at 10 Hz plotted against the pulse number in cells expressing hTRPV1 (D) and hTRPA1 (F) after the protocol described in figure 1D. (E, G) Bar diagrams displaying the effective inhibition of sodium currents at the last pulse after application of test substances. The peak amplitude of sodium currents activated after application of agonist ± QX-314 were normalized to the peak amplitudes of sodium currents determined at the first test pulse. Data are mean ± SD. n.s. = not significant, *P < 0.05, **P < 0.01, ***P < 0.001.