Modulation of calcium channels by metabotropic glutamate receptors in cerebellar granule cells.
We investigated the mechanisms by which metabotropic glutamate receptors (mGluRs) modulate specific Ca2+ channels in cerebellar granule cells. A large fraction of the current in granule cells is carried by L- and Q-type Ca2+ channels (about 26% each), whereas N- and P-type contribute proportionally less to the global current (9 and 15%, respectively). l-Aminocyclopentane-dicarboxylate (t-ACPD), (2S,3S,4S)-alpha-(carboxycyclopropyl)-glycine (L-CCGI) and (S)-4-carboxy-3-hydroxyphenylglycine [(S)-4C3HPG], but not L(+)-2-amino-4-phosphonobutyrate (L-AP4) reduced the Ca2+ current amplitude. The t-ACPD-induced inhibition was fully antagonized by (+/-)-methyl-4-carboxyphenylglycine [(+/-)-MCPG] and blocked by pertussis toxin (PTX). These results are consistent with inhibitory response mediated by mGluR2/R3. The use of specific Ca2+ channel blockers provided evidence that mGluR2/R3 inhibited both L- and N-type Ca2+ currents. In PTX-treated cells, Glu or t-ACPD, but not L-CCGI or L-AP4, increased the Ca2+ current. Consistent with the activation of mGluR1, the antagonists (+)-MCPG and (S)-4C3HPG prevented the facilitation of Ca2+ current produced by t-ACPD. The mGluR1-activated facilitation was completely blocked by nimodipine, indicating that L-type Ca2+ currents were selectively potentiated.
Chavis
P
P
CNRS UPR 9023, CCIPE, Montpellier, France.
Fagni
L
L
Bockaert
J
J
Lansman
J B
JB
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D046508:Culture Techniques; D004594:Electrophysiology; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018094:Receptors, Metabotropic Glutamate; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin