Turned On by a Drop in Calcium

Abstract

Smith et al. used patch-clamp analysis of cortical synaptosomes (pinched-off nerve terminals) to investigate the consequences of lowering extracellular calcium ([Ca 2+ ] o ), and they identified a nonselective cation channel activated by decreasing [Ca 2+ ] o . Neurotransmitter release is triggered by influx of calcium into the presynaptic nerve terminal; at excitatory central synapses, calcium may enter the postsynaptic neuron as well. Synaptic activity can thus lead to a reduction in [Ca 2+ ] o in the restricted extracellular volume of the synaptic cleft. Smith et al. used electron microscopy to verify that small clusters of synaptosomes plated on coverslips consisted mostly of nerve terminals. They also verified with the fluorescent dye FM-143 that synaptosomes underwent synaptic vesicle exocytosis and endocytosis in response to depolarization with elevated [K + ] o . In recording from synaptosome-attached patches, the authors found that reducing [Ca 2+ ] o unmasked a depolarization-dependent slow outward current activated by physiologically relevant decreases in synaptic [Ca 2+ ] o . Measurement of the reversal potential in inside-out patches under various ionic conditions indicated that this current was carried by a novel nonselective cation channel (NSC). The channel was indirectly inhibited by Gd 3+ , spermidine, and Mg 2+ , as well as by Ca 2+ , with a rank order of potency that matched that of the extracellular Ca 2+ receptor (CaR, a G protein-coupled receptor involved in regulating serum [Ca 2+ ] o ). Thus, activity-dependent reduction in synaptic [Ca 2+ ] is likely to lead--through an indirect mechanism--to enhanced activation of the NSC and thereby to modulation of the excitability of the presynaptic nerve terminal. S. M. Smith, J. B. Bergsman, N. C. Harata, R. H. Scheller, R. W. Tsien, Recordings from single neocortical nerve terminals reveal a nonselective cation channel activated by decreases in extracellular calcium. Neuron 41 , 243-256 (2004). [Online Journal]