Fine-tuning synaptic plasticity by modulation of CaV2.1 channels with Ca2+ sensor proteins

Modulation of P/Q-type Ca2+ currents through presynaptic voltage-gated calcium channels (Ca(V)2.1) by binding of Ca2+/calmodulin contributes to short-term synaptic plasticity. Ca2+-binding protein-1 (CaBP1) and Visinin-like protein-2 (VILIP-2) are neurospecific calmodulin-like Ca2+ sensor proteins that differentially modulate Ca(V)2.1 channels, but how they contribute to short-term synaptic plasticity is unknown. Here, we show that activity-dependent modulation of presynaptic Ca(V)2.1 channels by CaBP1 and VILIP-2 has opposing effects on short-term synaptic plasticity in superior cervical ganglion neurons. Expression of CaBP1, which blocks Ca2+-dependent facilitation of P/Q-type Ca2+ current, markedly reduced facilitation of synaptic transmission. VILIP-2, which blocks Ca2+-dependent inactivation of P/Q-type Ca2+ current, reduced synaptic depression and increased facilitation under conditions of high release probability. These results demonstrate that activity-dependent regulation of presynaptic Ca(V)2.1 channels by differentially expressed Ca2+ sensor proteins can fine-tune synaptic responses to trains of action potentials and thereby contribute to the diversity of short-term synaptic plasticity.