R- and L-type Ca2+ channels are insensitive to eliprodil in rat cultured cerebellar granule neurons.
We have investigated, by using the whole-cell patch-clamp technique, the Ca2+ channel antagonist properties of eliprodil in cultured cerebellar granule cells which are known to express L-, N-, P- as well as Q- and R-type Ca2+ channels. Eliprodil maximally antagonized 50% of the voltage-dependent Ba2+ current with an IC50 of 4 microM. omega-Conotoxin-GVIA (3.2 microM) and omega-agatoxin-IVA (0.5 microM) blocked 28 and 43% of the current, respectively. When eliprodil (30 microM) was added to omega-conotoxin-GVIA or omega-agatoxin-IVA the magnitude of the maximal inhibition was identical to that obtained with eliprodil alone confirming a full blockade by eliprodil of N-, P- and Q-type Ca2+ channels. The L-type channel antagonist nimodipine (10 microM) blocked 24% of the current; this blockade was fully additive to that of eliprodil, indicating that the nimodipine-sensitive component of the current is eliprodil-insensitive. In the presence of eliprodil and nimodipine a residual Cd2+ sensitive current (25%), identified as the R-type current, remained unblocked. We conclude that in cerebellar granule neurons R- and L-type Ca2+ channels are insensitive to eliprodil. The nimodipine-sensitive channels present in cerebellar granule neurons may represent a neuronal subtype of L channels distinct from that (eliprodil-sensitive/nimodipine-sensitive) present in cortical or hippocampal neurons.
Biton
B
B
Synthélabo Recherche, CNS Research Department, Bagneux, France.
Godet
D
D
Granger
P
P
Avenet
P
P
D000818:Animals; D001464:Barium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009553:Nimodipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D013111:Spider Venoms / Q000494:pharmacology; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D010880:Piperidines; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D001464:Barium; D009553:Nimodipine; D020866:omega-Conotoxin GVIA; C058083:eliprodil