boosting of synaptic potentials and spine ca transients by the peptide toxin snx-482 requires alpha-1e-encoded voltage-gated ca channels促进突触电位和脊柱钙瞬变的肽毒素snx - 482需要alpha-1e-encoded电压门控钙通道.pdfVIP

Boosting of Synaptic Potentials and Spine Ca Transients by the Peptide Toxin SNX-482 Requires Alpha-1E- Encoded Voltage-Gated Ca Channels Andrew J. Giessel, Bernardo L. Sabatini* Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, United States of America Abstract 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 CaV2.3, 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 CaV2.3 channel. Citation: Giessel AJ, Sabatini BL (2011) Boosting of Synaptic Potentials and Spine Ca Transients by the Peptide Toxin SNX-482 Requires Alpha-1E-Encoded Voltage-Gated Ca Channels. PLoS ONE 6(6): e20939. doi:10.1371/journal.pone.0020939 ´ ´ Editor: Olivier Jacques Manzoni, Institut National de la Sante et de la