%0 Journal Article
%A Ladera, Carolina
%A Martín Herranz, Ricardo
%A Bartolomé-Martín, David
%A Torres Molina, Magdalena Isabel
%A Sánchez-Prieto Borja, José
%T Partial compensation for N-type Ca2+ channel loss by P/Q-type Ca2+ channels underlines the differential release properties supported by these channels at cerebrocortical nerve terminals
%D 2009
%@ 0953-816X
%U https://hdl.handle.net/20.500.14352/98023
%X N-type and P/Q-type Ca2+ channels support glutamate release at central synapses. To determine whether the glutamate release mediated by these channels exhibits distinct properties, we have isolated each release component in cerebrocortical nerve terminals from wild-type mice by specifically blocking N-type Ca2+ channels with ω-conotoxin-GVIA and P/Q-type Ca 2+ channels with ω-agatoxin-IVA. In addition, we have determined the release properties at terminals from mice lacking the α1B subunit of N-type channels (Cav 2.2) to test the possibility that P/Q-type channels can compensate for the loss of N-type Ca2+ channels. We recently demonstrated that, while evoked glutamate release depends on P/Q- and N-type channels in wild-type nerve terminals, only P/Q-type channels participate in these knockout mice. Moreover, in nerve terminals expressing solely P/Q-type channels, metabotropic glutamate receptor 7 (mGluR7) fails to inhibit the evoked Ca2+ influx and glutamate release. Here, we show that the failure of mGluR7 to modulate evoked glutamate release is not due to a lack of receptors, as nerve terminals from mice lacking N-type Ca2+ channels express mGluR7. Indeed, we show that other receptor responses, such as the inhibition of forskolin-induced release, are preserved in these knockout mice. N-type channels are more loosely coupled to release than P/Q-type channels in nerve terminals from wild-type mice, as reflected by the tighter coupling of release in knockout nerve terminals. We conclude that the glutamate release supported by N- and P/Q-type channels exhibits distinct properties, and that P/Q-type channels cannot fully compensate for the loss of N-type channels. © 2009 Federation of European Neuroscience Societies and Blackwell.
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