Figure 7.

Calcium attenuates tachyphylaxis A, top, ASIC1a was repeatedly activated by pH 5 either with 0.1 mm extracellular Ca²⁺ (left) or with 10 mm extracellular Ca²⁺ (right). Bottom, current amplitudes were normalized to the first amplitude. Continuous lines represent fits to a single exponential function. Calcium attenuated tachyphylaxis: 0.1 Ca²⁺, n = 10; 1.8 Ca²⁺, n = 10; 10 Ca²⁺, n = 11. *P < 0.01, **P < 0.001 by ANOVA. B, top, ASIC1a was repeatedly activated by pH 5 either with 1.8 Ca²⁺–1.0 Mg²⁺ (left) or with 0 Ca²⁺–2.8 Mg²⁺ (right). Holding potential was 0 mV. Tachyphylaxis was enhanced when extracellular Ca²⁺ was replaced by Mg²⁺. n = 7 for 1.8 Ca²⁺–1.0 Mg²⁺ and n = 9 for 0 Ca²⁺–2.8 Mg²⁺. *P < 0.01, **P < 0.001 by t test. C, block of the ion pore by Ca²⁺ is not involved in tachyphylaxis. Top, ASIC1a mutant E425GD432C was repeatedly activated by pH 5 either with 1.8 mm (left) or with 10 mm extracellular Ca²⁺ (right). Extracellular concentration of Mg²⁺ was always 1 mm. Calcium attenuated tachyphylaxis as for ASIC1a wt: 1.8 Ca²⁺, n = 6; 10 Ca²⁺, n = 8. For direct comparison, the results for ASIC1a wt from Fig. 7A are shown as light symbols and the respective fits as dashed lines.