Cell Reports
Volume 20, Issue 2, 11 July 2017, Pages 333-343
Journal home page for Cell Reports

Article
Alternative Splicing of P/Q-Type Ca2+ Channels Shapes Presynaptic Plasticity

https://doi.org/10.1016/j.celrep.2017.06.055Get rights and content
Under a Creative Commons license
open access

Highlights

  • P/Q-type Ca2+ channel splice isoforms couple differentially to transmitter release

  • The balance between P/Q-type Ca2+ channel isoforms contributes to synaptic efficacy

  • Splicing of P/Q-type Ca2+ channels regulates short-term synaptic plasticity

  • Neurons control P/Q-type Ca2+ channel isoform levels in a homeostatic fashion

Summary

Alternative splicing of pre-mRNAs is prominent in the mammalian brain, where it is thought to expand proteome diversity. For example, alternative splicing of voltage-gated Ca2+ channel (VGCC) α1 subunits can generate thousands of isoforms with differential properties and expression patterns. However, the impact of this molecular diversity on brain function, particularly on synaptic transmission, which crucially depends on VGCCs, is unclear. Here, we investigate how two major splice isoforms of P/Q-type VGCCs (Cav2.1[EFa/b]) regulate presynaptic plasticity in hippocampal neurons. We find that the efficacy of P/Q-type VGCC isoforms in supporting synaptic transmission is markedly different, with Cav2.1[EFa] promoting synaptic depression and Cav2.1[EFb] synaptic facilitation. Following a reduction in network activity, hippocampal neurons upregulate selectively Cav2.1[EFa], the isoform exhibiting the higher synaptic efficacy, thus effectively supporting presynaptic homeostatic plasticity. Therefore, the balance between VGCC splice variants at the synapse is a key factor in controlling neurotransmitter release and presynaptic plasticity.

Keywords

P/Q-type voltage-gated calcium channels
Cav2.1
alternative splicing
short-term synaptic plasticity
release probability
homeostatic synaptic plasticity
optogenetics
synaptophysin-pHluorin
GCaMP
RNAi

Cited by (0)

7

Lead Contact