Modulation of the epithelial Ca2+ channel ECaC by extracellular pH

We investigated the effect of extracellular pH on whole-cell currents throu gh the epithelial Ca2+ channel, ECaC, expressed in HEK 293 cells. Both mono - and divalent current densities were significantly smaller at pH 6.0 than at pH 7.4. At pH 8.5 they were slightly larger. Lowering extracellular pH e nhanced the slow component of monovalent current activation at negative pot entials but had no significant effect on the kinetics of Ca2+ currents. The kinetics of block of monovalent cation current by extracellular Mg2+ was s ignificantly changed at high and low pH. The time constant of the time- and voltage-dependent current component during a voltage step to -140 mV was s ignificantly larger at pH 8.5 than at pH 7.4. At pH 6.0 it was almost absen t. The [Mg2+] inhibiting 50% of monovalent current through ECaC at pH 6.0 ( IC50) was 323 +/- 23 muM (n=8), compared with 62 +/-9 muM (n=4) at pH 7.4 a nd 38 +/-4 muM (n=8) at pH 8.5. The affinity of ECaC for Ca2+ was also affe cted by extracellular pH, shifting from 4.8 +/-0.7 muM (n=6) at pH 6.0 to 1 61 +/- 30 nM (n=5) at pH 7.4 and 425 +/- 117 nM (n=8) at pH 8.5.