Lidocaine activates and blocks rat TRPA1. A. Representative inward currents in HEK293t cells expressing rTRPA1 activated by 30 mM lidocaine and 100 μM mustard oil. Cells were held at -60 mV. B- C. Concentration dependent activation of rTRPA1 by lidocaine. Only one concentration was applied on each cell. The Hill-equation was applied to calculate the EC50 value. D. A typical example of a lidocaine-evoked current blocked by the selective TRPA1-anatagonist HC-030331 (100 μM). E. Ramp currents of rTRPA1 in control solution and during application of 30 mM lidocaine. Cells were held at -60 mV and currents were measured during 500 ms long voltage-ramps from -100 to +100 mV. Note the lack of an outward rectification of the lidocaine-evoked current F. Representative effects on rTRPA1 30 mM lidocaine in cells held at +60 mV..G. Typical MO-evoked inward current blocked by 100 mM lidocaine. Increasing concentrations of lidocaine were co-applied with MO during the steady-state phase of MO-evoked currents. Experiments were performed in a Ca2+-free extracellular solution to minimize desensitization. The fractional block was plotted against the lidocaine concentration. The line represents the fit of the data to the Hill equation. H. Representative currents of TRPA1-currents activated by three consecutive applications of 30 mM lidocaine in standard extracellular solution containing 2 mM Ca2+. Lidocaine was applied in intervals of 2 min. I. Mean current amplitudes of rTRPA1 currents evoked by repeated applications of lidocaine in standard extracellular solution containing 2 mM Ca2+ or in a Ca2+-free solution. Current amplitudes are normalized to the value obtained with the first application of lidocaine (dotted line).