Recordings from Single Neocortical Nerve Terminals Reveal a Nonselective Cation Channel Activated by Decreases in Extracellular Calcium

Abstract Synaptic activity causes reductions in cleft [Ca 2+ ] 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 [Ca 2+ ] ([Ca 2+ ] 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, Gd 3+ > spermidine > Ca 2+ > Mg 2+ , typical for [Ca 2+ ] o receptors). The identification of a Ca 2+ sensor-NSC channel pathway establishes the existence of a mechanism by which presynaptic terminals can detect and respond to reductions in cleft [Ca 2+ ]. 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.