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

GIUGOVAZ-TROPPER B; GONZALEZ-INCHAUSPE C; DI GUILMI MN; URBANO FJ; FORSHYTE ID; UCHITEL OD

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2011 vol. 192 p. 219 - 230

0306-4522

Cav2.1 channels (P/Q type) play a prominent role in controlling neurotransmitter release. Transgenic mice in which the α1A pore-forming subunit of Cav2.1 channels is ablated (KO) provide a powerful tool to study Cav2.1 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 Ca2+ channels, in opposition to synapses where only this type of Ca2+ channels are in charge of transmitter release. We found that in KO mice, N-type and L-type Ca2+ channels control synaptic transmission, resulting in a functional but reduced glycinergic transmitter release. Paired 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-gamma-aminobutyric acid type B (GABA-B).