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Published online July 30, 2007
doi:10.1083/jcb.200702072
The Journal of Cell Biology, Vol. 178, No. 3, 489-502
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Xie et al.
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Article

 Facilitation versus depression in cultured hippocampal neurons determined by targeting of Ca2+ channel Cavß4 versus Cavß2 subunits to synaptic terminals

Mian Xie, Xiang Li, Jing Han, Daniel L. Vogt, Silke Wittemann, Melanie D. Mark, and Stefan Herlitze

Department of Neurosciences, Case Western Reserve University, Cleveland, OH 44106

Correspondence to Stefan Herlitze: sxh106{at}cwru.edu

Ca2+ channel ß subunits determine the transport and physiological properties of high voltage–activated Ca2+ channel complexes. Our analysis of the distribution of the Cavß subunit family members in hippocampal neurons correlates their synaptic distribution with their involvement in transmitter release. We find that exogenously expressed Cavß4b and Cavß2a subunits distribute in clusters and localize to synapses, whereas Cavß1b and Cavß3 are homogenously distributed. According to their localization, Cavß2a and Cavß4b subunits modulate the synaptic plasticity of autaptic hippocampal neurons (i.e., Cavß2a induces depression, whereas Cavß4b induces paired-pulse facilitation [PPF] followed by synaptic depression during longer stimuli trains). The induction of PPF by Cavß4b correlates with a reduction in the release probability and cooperativity of the transmitter release. These results suggest that Cavß subunits determine the gating properties of the presynaptic Ca2+ channels within the presynaptic terminal in a subunit-specific manner and may be involved in organization of the Ca2+ channel relative to the release machinery.

Abbreviations used in this paper: AP, action potential; EPSC, excitatory postsynaptic current; PPF, paired-pulse facilitation; PPR, paired-pulse ratio; RRP, readily releasable vesicle pool; SFV, Semliki Forest virus.


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