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, Supporting information for: From identification to functional characterization of cyriotoxin-1a, an antinociceptive toxin from Cyriopagopus schioedtei spider

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, each consisting of a 50-ms step to the voltage of the peak current of the current-voltage relationship for each channel, were applied at 10 Hz (50-ms interpulse interval). The current signal was sampled at 10 kHz. Currents were leak-subtracted based on the estimate of current evoked during the -10 mV step at the start of the voltage pulse protocol. Pre-and postcompound sodium current amplitudes were measured automatically from the leak-subtracted traces by the IonWorks software through averaging a 10 ms current during the initial holding period at -90 mV (baseline current) and subtracting this from the peak of the current response for each of the eight voltage steps, pre-and post-compound responses were evoked by a voltage train as follows: after a 10-sec period holding at -120 mV, ten pulses

. Bell, Venom fractions and sub-fractions, as well as CyrTx-1a, were diluted in the extracellular medium supplemented with bovine serum albumin (0.1%), to give the final concentrations indicated in the text. The times of incubation varied between ~2 and ~7 min to achieve steady-state effects. The experiments were carried out at room temperature (20-22°C). The hNa V -overexpressing HEK-293 cells were maintained at a holding potential of either -90 mV (hNa V 1.5) or -100 mV (other hNa V channel subtypes). Currents were elicited at a frequency of 0.2 Hz (at least 4.78-s interpulse interval) by 20-ms test-pulses to -20 mV (hNa V 1.1, 1.2, 1.4, and 1.7), -10 mV (hNa V 1.3), -40 mV (hNa V 1.5), -15 mV (hNa V 1.6) or +10 mV (hNa V 1.8), preceded by 200-ms (hNa V 1.5) or 40-ms (hNa V 1.7) pulses to -120 mV, or not (hNa V 1.1, 1.2, 1.3, 1.4 and 1.6). The hCa V -overexpressing CHO cells were maintained at a holding potential of -50 mV (hCa V 1.2) or -100 mV (hCa V 3.1 and 3.2), and currents were elicited at a frequency of 0.05 Hz (at least 19.5-s interpulse interval) by 200-ms test-pulses to +0 mV (hCa V 1.2) or by 500-ms test-pulses to -20 mV (hCa V 3.1 and 3.2). The hK V 11.1-overexpressing CHO cells were maintained at a holding potential of -80 mV, Filters were set to a pre-scan seal resistance of 40 M?, pre-scan hNa V 1.7 current amplitude of 200 pA, and post-scan seal resistance of 40 M?. Cells that did not meet these criteria were discarded from the measurements. Dividing the post-scan current amplitude by the respective pre-scan current amplitude for each well assessed the degree of inhibition of the hNa V 1.7 current. Secondary screening for hit confirmation, as well as rapid selectivity check, were also performed on an automated patch-clamp system, the QPatch HTX (Sophion Bioscience, Denmark) recording currents in whole-cell configuration, allowing both signal acquisition and data analyses, vol.4, pp.2312-2321, 2018.

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