Blockage of the open pore reduces tachphylaxis A, top, ASIC1a was repeatedly activated with pH 4 either in the absence or in the presence of amiloride, as indicated. Bottom, current amplitudes were normalized to the first amplitude. Continuous line represents a fit to a single exponential function. For the series to assess the effect of amiloride, only the amplitudes of the amiloride-free applications (1st and 7th) are shown. n = 12 without amiloride and n = 9 with amiloride. **P < 0.001 by t test. B, outward currents do show tachyphylaxis. Top, representative traces of ASIC1a outward currents. Extracellular ion concentrations were (mm): 130 NMDGCl, 10 NaCl, 1.8 CaCl2, 1.0 MgCl2, 10 Hepes, pH 7.4. For acidic activation solution (pH 5.0), Hepes was replaced by Mes. Holding potential was +20 mV during the test period. n = 9.