Changes in synaptic transmission properties due to the expression of N-type calcium channels at the calyx of Held synapse of mice lacking P/Q-type calcium channels

CARLOTA GONZÁLEZ INCHAUSPE; IAN D. FORSYTHE; OSVALDO D. UCHITEL

THE JOURNAL OF PHYSIOLOGY

Blackwell Publishing Ltd

Año: 2007 vol. 584. p. 835 - 851

0022-3751

P/Q-type and N-type calcium channels mediate transmitter release at rapidly transmittingcentral synapses, but the reasons for the specific expression of one or the other in each particularsynapse are not known. Using whole-cell patch clamping from in vitro slices of the auditorybrainstem we have examined presynaptic calcium currents (IpCa) and glutamatergic excitatorypostsynaptic currents (EPSCs) at the calyx of Held synapse from transgenic mice in whichthe α1A pore-forming subunit of the P/Q-type Ca2+ channels is ablated (KO). The powerrelationship between Ca2+ influx and quantal output was studied by varying the number ofCa2+ channels engaged in triggering release. Our results have shown that more overlappingCa2+ channel domains are required to trigger exocytosis when N-type replace P/Q-type calciumchannels suggesting that P/Q type Ca2+ channels are more tightly coupled to synaptic vesiclesthan N-type channels, a hypothesis that is verified by the decrease in EPSC amplitudes inKO synapses when the slow Ca2+ buffer EGTA-AM was introduced into presynaptic calyces.Significant alterations in short-term synaptic plasticity were observed. Repetitive stimulationat high frequency generates short-term depression (STD) of EPSCs, which is not caused bypresynaptic Ca2+ current inactivation neither in WT or KO synapses. Recovery after STD ismuch slower in the KO than in the WT mice. Synapses from KO mice exhibit reduced or noEPSC paired-pulse facilitation and absence of facilitation in their presynaptic N-type Ca2+currents. Simultaneous pre- and postsynaptic double patch recordings indicate that presynapticCa2+ current facilitation is the main determinant of facilitation of transmitter release. Finally,KO synapses reveal a stronger modulation of transmitter release by presynaptic GTP-bindingprotein-coupled receptors (γ-aminobutyric acid type B receptors, GABAB, and adenosine). Incontrast, metabotropic glutamate receptors (mGluRs) are not functional at the synapses of thesemice. These experiments reinforce the idea that presynaptic Ca2+ channels expression may betuned for speed and modulatory control through differential subtype expression.