Boosting of synaptic potentials and spine Ca transients by the peptide toxin SNX-482 requires alpha-1E-encoded voltage-gated Ca channels

• Published in: PloS one Vol. 6; no. 6; p. e20939
• Main Authors: Giessel, Andrew J, Sabatini, Bernardo L
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09-06-2011; Public Library of Science (PLoS)
• Subjects: Animals; Biology; Calcium; Calcium - metabolism; Calcium channels; Calcium channels (voltage-gated); Calcium Channels, R-Type - deficiency; Calcium Channels, R-Type - genetics; Calcium Channels, R-Type - metabolism; Calcium conductance; Cation Transport Proteins - deficiency; Cation Transport Proteins - genetics; Cation Transport Proteins - metabolism; Central nervous system; Dendritic spines; Dendritic Spines - drug effects; Dendritic Spines - metabolism; Electric potential; Gene Knockout Techniques; Glutamate; Glutamatergic transmission; Glutamic acid receptors (ionotropic); Hippocampus; Ion channels; Lasers; Mice; N-Methyl-D-aspartic acid receptors; Neurobiology; Neurons; Neurophysiology; Neurosciences; Peptides; Peptides - pharmacology; Pharmacology; Pore formation; Potassium; Potassium channels; Potassium channels (calcium-gated); Potassium channels (voltage-gated); Potassium conductance; Proteins; Protuberances; Receptors; Resistance; Rodents; Signal Transduction - drug effects; Signaling; Spider Venoms - pharmacology; Spine; Synapses; Synaptic Potentials - drug effects; United States > US; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0020939

The majority of glutamatergic synapses formed onto principal neurons of the mammalian central nervous system are associated with dendritic spines. Spines are tiny protuberances that house the proteins that mediate the response of the postsynaptic cell to the presynaptic release of glutamate. Postsynaptic signals are regulated by an ion channel signaling cascade that is active in individual dendritic spines and involves voltage-gated calcium (Ca) channels, small conductance (SK)-type Ca-activated potassium channels, and NMDA-type glutamate receptors. Pharmacological studies using the toxin SNX-482 indicated that the voltage-gated Ca channels that signal within spines to open SK channels belong to the class Ca(V)2.3, which is encoded by the Alpha-1E pore-forming subunit. In order to specifically test this conclusion, we examined the effects of SNX-482 on synaptic signals in acute hippocampal slices from knock-out mice lacking the Alpha-1E gene. We find that in these mice, application of SNX-482 has no effect on glutamate-uncaging evoked synaptic potentials and Ca influx, indicating that that SNX-482 indeed acts via the Alpha-1E-encoded Ca(V)2.3 channel.