title: P/Q-type calcium channel ablation in a mice glycinergic synapse mediated by multiple types of Ca²+ channels alters transmitter release and short term plasticity.
abstract: Ca(v)2.1 channels (P/Q-type) play a prominent role in controlling neurotransmitter release. Transgenic mice in which the α1A pore-forming subunit of Ca(v)2.1 channels is ablated (KO) provide a powerful tool to study Ca(v)2.1 function in synaptic transmission in vivo. Whole-cell patch clamp was used to measure inhibitory glycinergic postsynaptic currents (IPSCs) from the lateral superior olive (LSO). Comparing wild-type (WT) and KO mice, we investigated the relevance of P/Q-type calcium channels at a glycinergic synapse mediated by multiple types of Ca(2+) channels, in opposition to synapses where only this type of Ca(2+) channels are in charge of transmitter release. We found that in KO mice, N-type and L-type Ca(2+) channels control synaptic transmission, resulting in a functional but reduced glycinergic transmitter release. Pair pulse facilitation of synaptic currents is retained in KO mice, even when synaptic transmission is driven by either N or L-type calcium channels alone, in contrast with lack of this phenomenon in other synapses which are exclusively mediated by P/Q-type channels. Thus, pointing a difference between P/Q- and N-type channels present in single or multiple types of calcium channels driven synapses. Significant alterations in short-term synaptic plasticity were observed. KO mice exhibited a stronger short term depression (STD) of IPSCs during repetitive stimulation at high frequency and recovered with a larger time constant compared to WT mice. Finally, transmitter release at the LSO synapse from KO mice was strongly modulated by presynaptic GTP-binding protein-coupled receptor γ-aminobutyric acid type B (GABA(B)).
authors: Instituto de Fisiología, Biología molecular y Neurociencias, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, 1428, Buenos Aires, Argentina.
authors: B
authors: B
authors: Giugovaz-Tropper
authors: C
authors: C
authors: González-Inchauspe
authors: M N
authors: MN
authors: Di Guilmi
authors: F J
authors: FJ
authors: Urbano
authors: I D
authors: ID
authors: Forsythe
authors: O D
authors: OD
authors: Uchitel
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D020865:Calcium Channels, P-Type / Q000378:metabolism*; D020907:Calcium Channels, Q-Type / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005998:Glycine / Q000378:metabolism; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D018377:Neurotransmitter Agents; D005998:Glycine