Extracellular calcium sensed by a novel cation channel in hippocampal neurons

Extracellular concentrations of Ca(2+) change rapidly and transiently in the brain during excitatory synaptic activity. To test whether such changes in Ca(2+) can play a signaling role we examined the effects of rapidly lowering Ca(2+) on the excitability of acutely isolated CA1 and cultured hippocampal neurons. Reducing Ca(2+) excited and depolarized neurons by activating a previously undescribed nonselective cation channel. This channel had a single-channel conductance of 36 pS, and its frequency of opening was inversely proportional to the concentration of Ca(2+). The inhibition of gating of this channel was sensitive to ionic strength but independent of membrane potential. The ability of this channel to sense Ca(2+) provides a novel mechanism whereby neurons can respond to alterations in the extracellular concentration of this key signaling ion.