title: Partial compensation for N-type Ca(2+) channel loss by P/Q-type Ca(2+) channels underlines the differential release properties supported by these channels at cerebrocortical nerve terminals.
abstract: N-type and P/Q-type Ca(2+) 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 Ca(2+) channels with omega-conotoxin-GVIA and P/Q-type Ca(2+) channels with omega-agatoxin-IVA. In addition, we have determined the release properties at terminals from mice lacking the alpha(1B) subunit of N-type channels (Ca(v) 2.2) to test the possibility that P/Q-type channels can compensate for the loss of N-type Ca(2+) 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 Ca(2+) 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 Ca(2+) 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.
authors.affiliation: Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Ladera
authors.forename: Ricardo
authors.initials: R
authors.lastname: Martín
authors.forename: David
authors.initials: D
authors.lastname: Bartolomé-Martín
authors.forename: Magdalena
authors.initials: M
authors.lastname: Torres
authors.forename: José
authors.initials: J
authors.lastname: Sánchez-Prieto
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000172:deficiency*; D020865:Calcium Channels, P-Type / Q000378:metabolism*; D020907:Calcium Channels, Q-Type / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology*; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005089:Exocytosis / Q000187:drug effects / Q000235:genetics; D055786:Gene Knockout Techniques; D018698:Glutamic Acid / Q000378:metabolism; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D018094:Receptors, Metabotropic Glutamate / Q000145:classification / Q000235:genetics; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D000613:Aminobutyrates; C500963:Cacna1b protein, mouse; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D016376:Oligonucleotides, Antisense; D010703:Phorbol Esters; D026902:Potassium Channel Blockers; D018094:Receptors, Metabotropic Glutamate; D005576:Colforsin; D018698:Glutamic Acid; D015761:4-Aminopyridine; C012729:2-amino-4-phosphonobutyric acid; D002118:Calcium