Figure 4

Potentiation of ASIC1a/2a by PcTx1 in rat cortical neurons. (a) Traces of pH6.8-induced membrane depolarization from a single neuron in the absence and presence of PcTx1. (b and c) Time courses of PcTx1 modulation for the same neuron as in (a). The dotted lines at the bottom represent the baseline. Note the dip in membrane potential to below that in the presence of 10 nM PcTx1 upon initial wash of 10 nM (b) and 100 nM (c) PcTx1. (d) Averages of pH6.8-induced depolarization from multiple neurons (n = 8, 4, 8 and 8 for 0, 1, 10 and 100 nM PcTx1, respectively). The horizontal dashed line represents the value in the presence of 10 nM PcTx1. PcTx1 was applied in the order of increasing concentration and the wash data were recorded upon wash-off of 100 nM PcTx1. (e) Traces of pH6.8-induced current from a single neuron in the absence and presence of PcTx1. (f) Time course of PcTx1 modulation from the same neuron as in (e). The dotted line at the top represents the baseline. Note the lower current amplitude than that in the presence of 10 nM PcTx1 upon first removal of 100 nM PcTx1. (g) Averages of pH6.8-induced currents from multiple neurons (n = 10 each for 0, 10 and 100 nM PcTx1, respectively). The horizontal dashed line represents the value in the presence of 10 nM PcTx1. PcTx1 was applied in the order of increasing concentration and the wash data were recorded upon wash-off of 100 nM PcTx1. For all the experiments in Fig. 4, the conditioning pH was 7.4 and the test pH of 6.8 was applied for 2–3 sec before returning to pH7.4. This pH application protocol was repeated once every 60 sec.