title: Fine-tuning synaptic plasticity by modulation of Ca(V)2.1 channels with Ca2+ sensor proteins.
abstract: Modulation of P/Q-type Ca(2+) currents through presynaptic voltage-gated calcium channels (Ca(V)2.1) by binding of Ca(2+)/calmodulin contributes to short-term synaptic plasticity. Ca(2+)-binding protein-1 (CaBP1) and Visinin-like protein-2 (VILIP-2) are neurospecific calmodulin-like Ca(2+) 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 Ca(2+)-dependent facilitation of P/Q-type Ca(2+) current, markedly reduced facilitation of synaptic transmission. VILIP-2, which blocks Ca(2+)-dependent inactivation of P/Q-type Ca(2+) 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 Ca(2+) sensor proteins can fine-tune synaptic responses to trains of action potentials and thereby contribute to the diversity of short-term synaptic plasticity.
authors.affiliation: Graduate Program in Neurobiology and Behavior, University of Washington, Seattle, WA 98195, USA.
authors.forename: Karina
authors.initials: K
authors.lastname: Leal
authors.forename: Sumiko
authors.initials: S
authors.lastname: Mochida
authors.forename: Todd
authors.initials: T
authors.lastname: Scheuer
authors.forename: William A
authors.initials: WA
authors.lastname: Catterall
mesh_terms: D000704:Analysis of Variance; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D006801:Humans; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D020864:Calcium Channels, N-Type; D002147:Calmodulin