title: Synapse-to-synapse variation of calcium channel subtype contributions in large mossy fiber terminals of mouse hippocampus.
abstract: Both N- and P/Q-type voltage-dependent calcium channels are involved in fast transmitter release in the hippocampus, but are differentially regulated. Although variable contributions of voltage-dependent calcium channel subtypes to presynaptic Ca2+ influx have been suggested to give a neural network of great diversity, their presence has only been demonstrated in a culture system and has remained unclear in the brain. Here, the individual large mossy fiber presynaptic terminal was labeled with Ca2+/Sr2+-sensitive fluorescent dextrans in the hippocampal slice of the mouse. The fractional contribution of voltage-dependent calcium channel subtypes to presynaptic Ca2+/Sr2+ influx was directly measured by the sensitivity of Ca2+/Sr2+-dependent fluorescent increment to subtype-selective neurotoxins, omega-conotoxin GVIA (an N-type selective blocker), omega-agatoxin IVA (a P/Q-type selective blocker) and SNX-482 (an R-type selective blocker). Synapse-to-synapse comparison of large mossy fiber terminals revealed that the contributions of N- and R-type voltage-dependent calcium channels varied more widely than that of P/Q-type. Even two large mossy fiber presynaptic terminals neighboring on the same axon differed in the fractional contributions of N- and R-type voltage-dependent calcium channels. On the other hand, these terminals were similar in the fractional contributions of P/Q-type voltage-dependent calcium channels. These results provide direct evidence that individual large mossy fiber synapses are differential in the contribution of N- and R-type voltage-dependent calcium channel subtypes to presynaptic Ca2+/Sr2+ influx. We suggest that the synapse-to-synapse variation of presynaptic voltage-dependent calcium channel subtype contributions may be one of the mechanisms amplifying diversity of the hippocampal network.
authors.affiliation: Department of Developmental Biology and Neurosciences, Tohoku University Graduate School of Life Sciences, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Miyazaki
authors.forename: T
authors.initials: T
authors.lastname: Ishizuka
authors.forename: H
authors.initials: H
authors.lastname: Yawo
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000145:classification / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D017729:Presynaptic Terminals / Q000502:physiology*; D011336:Probability; D021122:Protein Subunits; D013324:Strontium / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D021122:Protein Subunits; D002104:Cadmium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium; D013324:Strontium