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This Article Full Text Full Text (PDF) Supplemental data All Versions of this Article: 584/3/835    most recent jphysiol.2007.139683v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Inchauspe, C. G. Articles by Uchitel, O. D. Search for Related Content PubMed PubMed Citation Articles by Inchauspe, C. G. Articles by Uchitel, O. D. Related Collections Neuroscience

¹ Instituto de Fisiología, Biología molecular y Neurociencias. CONICET, Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina
² Cellular & Molecular Neuroscience, MRC Toxicology Unit, University of Leicester, Leicester LE1 9HN, UK

P/Q-type and N-type calcium channels mediate transmitter release at rapidly transmitting central synapses, but the reasons for the specific expression of one or the other in each particular synapse are not known. Using whole-cell patch clamping from in vitro slices of the auditory brainstem we have examined presynaptic calcium currents (I_pCa) and glutamatergic excitatory postsynaptic currents (EPSCs) at the calyx of Held synapse from transgenic mice in which the _1A pore-forming subunit of the P/Q-type Ca²⁺ channels is ablated (KO). The power relationship between Ca²⁺ influx and quantal output was studied by varying the number of Ca²⁺ channels engaged in triggering release. Our results have shown that more overlapping Ca²⁺ channel domains are required to trigger exocytosis when N-type replace P/Q-type calcium channels suggesting that P/Q type Ca²⁺ channels are more tightly coupled to synaptic vesicles than N-type channels, a hypothesis that is verified by the decrease in EPSC amplitudes in KO synapses when the slow Ca²⁺ buffer EGTA-AM was introduced into presynaptic calyces. Significant alterations in short-term synaptic plasticity were observed. Repetitive stimulation at high frequency generates short-term depression (STD) of EPSCs, which is not caused by presynaptic Ca²⁺ current inactivation neither in WT or KO synapses. Recovery after STD is much slower in the KO than in the WT mice. Synapses from KO mice exhibit reduced or no EPSC paired-pulse facilitation and absence of facilitation in their presynaptic N-type Ca²⁺ currents. Simultaneous pre- and postsynaptic double patch recordings indicate that presynaptic Ca²⁺ current facilitation is the main determinant of facilitation of transmitter release. Finally, KO synapses reveal a stronger modulation of transmitter release by presynaptic GTP-binding protein-coupled receptors (-aminobutyric acid type B receptors, GABA_B, and adenosine). In contrast, metabotropic glutamate receptors (mGluRs) are not functional at the synapses of these mice. These experiments reinforce the idea that presynaptic Ca²⁺ channels expression may be tuned for speed and modulatory control through differential subtype expression.

(Received 27 June 2007; accepted after revision 31 August 2007; first published online 6 September 2007)
Corresponding author O. D. Uchitel: Instituto de Fisiología, Biología molecular y Neurociencias. CONICET, Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina. Email: odu{at}fbmc.fcen.uba.ar