Recordings from single neocortical nerve terminals reveal a nonselective cation channel activated by decreases in extracellular calcium

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+], 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 [Ca2+](o) would be expected during periods of high activity in the neocortex and may modulate the excitability of the presynaptic terminal.