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

Publication date: 11 July 2017
Source:Cell Reports, Volume 20, Issue 2
Author(s): Agnes Thalhammer, Andrea Contestabile, Yaroslav S. Ermolyuk, Teclise Ng, Kirill E. Volynski, Tuck Wah Soong, Yukiko Goda, Lorenzo A. Cingolani
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.

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Teaser

Alternative splicing of Ca²⁺ channels has been hypothesized to contribute to functional diversity in the brain. Thalhammer et al. find that two splice isoforms of P/Q-type Ca²⁺ channels differentially regulate presynaptic plasticity. These results provide evidence that the balance between Ca²⁺ channel isoforms controls synaptic efficacy.


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