Calcium control of transmitter release at a cerebellar synapse.
The manner in which presynaptic Ca2+ influx controls the release of neurotransmitter was investigated at the granule cell to Purkinje cell synapse in rat cerebellar slices. Excitatory postsynaptic currents were measured using whole-cell voltage clamp, and changes in presynaptic Ca2+ influx were determined with the Ca(2+)-sensitive dye furaptra. We manipulated presynaptic Ca2+ entry by altering external Ca2+ levels and by blocking Ca2+ channels with Cd2+ or with the toxins omega-conotoxin GVIA and omega-Aga-IVA. For all of the manipulations, other than the application of omega-Aga-IVA, the relationship between Ca2+ influx and release was well approximated by a power law, n approximately 2.5. When omega-Aga-IVA was applied, release appeared to be more steeply dependent on Ca2+ (n approximately 4), suggesting that omega-Aga-IVA-sensitive channels are more effective at triggering release. Based on interactive effects of toxins on synaptic currents, we conclude that multiple types of Ca2+ channels synergistically control individual release sites.
Mintz
I M
IM
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Sabatini
B L
BL
Regehr
W G
WG
D000818:Animals; D001572:Benzofurans; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002531:Cerebellum / Q000502:physiology*; D004553:Electric Conductivity; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010080:Oxazoles; D010455:Peptides / Q000494:pharmacology; D011689:Purkinje Cells / Q000502:physiology; D051381:Rats; D013111:Spider Venoms / Q000494:pharmacology; D013569:Synapses / Q000502:physiology*; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D001572:Benzofurans; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D005456:Fluorescent Dyes; D018377:Neurotransmitter Agents; D010080:Oxazoles; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D002104:Cadmium; C058776:2-(2-(5-carboxy)oxazole)-5-hydroxy-6-aminobenzofuran-N,N,O-triacetic acid; D020866:omega-Conotoxin GVIA; D002118:Calcium; D016257:Fura-2