Recordings from single neocortical nerve terminals reveal a nonselective cation channel activated by decreases in extracellular calcium.
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.
Smith
Stephen M
SM
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, CA 94305, USA.
Bergsman
Jeremy B
JB
Harata
Nobutoshi C
NC
Scheller
Richard H
RH
Tsien
Richard W
RW
D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology; D002413:Cations, Divalent / Q000494:pharmacology; D005110:Extracellular Space / Q000502:physiology; D005470:Fluorometry; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D008854:Microscopy, Electron; D019579:Neocortex / Q000166:cytology / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000502:physiology*; D044169:Receptors, Calcium-Sensing / Q000502:physiology; D013574:Synaptosomes / Q000378:metabolism / Q000502:physiology
D002413:Cations, Divalent; D007473:Ion Channels; D018377:Neurotransmitter Agents; D044169:Receptors, Calcium-Sensing; D002118:Calcium