Cultured hippocampal neurons were initially perfused with bath solution containing 2.0 mM [Ca2+]o at pH 7.5. A, example traces showing the interaction between low pH- and low [Ca2+]o-mediated responses. At a holding potential of −60 mV, a step decrease of [Ca2+]0 from 2.0 to 0.1 mM activated a slow and sustained inward current through the csNSC channels (left panel), while a step decrease of pH from 7.5 to 6.5 activated a transient inward current, probably through proton-gated channels (middle panel). Simultaneous decreases in pH and [Ca2+]0 activated a much larger inward current (right panel). B, superimposed traces (left panel) and bar graph (right panel) showing the synergism between low pH- and low [Ca2+]0-induced responses. ** P < 0.01.