Synaptic activity causes reductions in cleft [Ca2+] that may impact subsequent synaptic efficacy. Using modified patch-clamp techniques to record from single neocortical nerve terminals, we report that physiologically relevant reductions of extracellular [Ca2+] ([Ca2+] o) activate voltage-dependent outward currents. These outward currents are carried by a novel nonselective cation (NSC) channel that is indirectly inhibited by various extracellular agents (rank order potency, Gd3+ > spermidine > Ca2+ > Mg2+, typical for [Ca2+]o receptors). The identification of a Ca2+ sensor-NSC channel pathway establishes the existence of a mechanism by which presynaptic terminals can detect and respond to reductions in cleft [Ca2+]. Activation of NSC channels by falls in [Ca 2+]o would be expected during periods of high activity in the neocortex and may modulate the excitability of the presynaptic terminal.
Smith, S. M., Bergsman, J. B., Harata, N. C., Scheller, R. H., & Tsien, R. W. (2004). Recordings from Single Neocortical Nerve Terminals Reveal a Nonselective Cation Channel Activated by Decreases in Extracellular Calcium. Neuron, 41(2), 243–256. https://doi.org/10.1016/S0896-6273(03)00837-7