Figure 8.

Single channel conductance of hERG1a E575Q/H578N is resistant to extracellular acidosis. (a) Representative traces of single hERG1a E575Q/H578N channels at -80 mV, recorded with a pipette solution pH of 7.4 (upper panel, 2 traces from a single recording) and pH 6.3 (lower panel, 2 traces from a single recording). Channel openings were evoked by a prepulse to +20 mV (V_H −80 mV) and observed following repolarization to -80 mV. Horizontal scale bar represents 500 ms and vertical scale bar represents 1 pA. (b) Single channel current-voltage relationship of hERG1a E575Q/H578N channels in pH 7.4 (•) and 6.3 (○). Channel conductance was not affected by extracellular acidosis, with a slope conductance of 11.7 ± 0.4 pS for pH 7.4 (n = 5 cells) and 12.0 ± 0.5 pS for pH 6.3 (n = 6 cells; P = 0.7032, unpaired student’s t-test). (ci) Open-time duration histogram derived from 5 patches with at pH 7.4. Channel activity at -80 mV was fit with a single exponential function with time constant 5.9 ms. (cii). Open duration histogram from 6 patches with at pH 6.3. Channel activity at −80 mV was not affected by acidic pH, being fit with a single exponential component with time constant 5.7 ms. (d) The voltage dependence of hERG1a-E575Q/H578N channel open time was not affected by pH_e. Plots were fit with an exponential function for both pH 7.4 (n = 5 cells) and pH 6.3 (n = 6 cells). No significance was observed between pH and membrane potential (two-way ANOVA with Bonferroni post-test).