Store-operated Ca2+-channels are sensitive to changes in extracellular pH

The sensitivity of store-operated Ca2+-entry to changes in the extra- and intracellular pH (pHo and pHi, respectively) was investigated in SH-SY5Y human neuroblastoma cells. The intracellular Ca2+-stores were depleted either with 1 mM carbachol (CCH) or with 2 μM thapsigargin (TG). Extracellular acidification suppressed both the CCH- and TG-mediated Ca2+-entry while external alkalinization augmented both the CCH- and the TG-induced Ca2+-influx. Mn2+-quenching experiments revealed that the rates of Ca2+-entry at the thapsigargin- or carbachol-induced plateau were both accelerated at pHo 8.2 and slowed down at pHo 6.8 with respect to the control at pHo 7.4. Alteration of pHo between 6.8 and 8.2 did not have any significant prompt effect on pHi and changes in pHi left the CCH-induced Ca2+-entry unaffected. These findings demonstrate that physiologically relevant changes in pHo affect the store-operated Ca2+-entry in SH-SY5Y cells and suggest that endogenous pHo shifts may regulate cell activity in situ via modulating the store-operated Ca2+-entry.