title: Developmental changes in Ca2+ channel subtypes regulating endocytosis at the calyx of Held.
abstract: At the mammalian central synapse, Ca(2+) influx through Ca(2+) channels triggers neurotransmitter release by exocytosis of synaptic vesicles, which fuse with the presynaptic membrane and are subsequently retrieved by endocytosis. At the calyx of Held terminal, P/Q-type Ca(2+) channels mainly mediate exocytosis, while N- and R-type channels have a minor role in young terminals (postnatal days 8-11). The role of each Ca(2+) channel subtype in endocytosis remains to be elucidated; therefore, we examined the role of each type of Ca(2+) channel in endocytosis, by using whole-cell patch-clamp recordings in conjunction with capacitance measurement techniques. We found that at the young calyx terminal, when R-type Ca(2+) channels were blocked, the slow mode of endocytosis was further slowed, while blocking of either P/Q- or N-type Ca(2+) channels had no major effect. In more mature terminals (postnatal days 14-17), the slow mode of endocytosis was mainly triggered by P/Q-type Ca(2+) channels, suggesting developmental changes in the regulation of the slow mode of endocytosis by different Ca(2+) channel subtypes. In contrast, a fast mode of endocytosis was observed after strong stimulation in young terminals that was mediated mainly by P/Q-type, but not R- or N-type Ca(2+) channels. These results suggest that different types of Ca(2+) channels regulate the two different modes of endocytosis. The results may also suggest that exo- and endocytosis are regulated independently at different sites in young animals but are more tightly coupled in older animals, allowing more efficient synaptic vesicle cycling adapted for fast signalling.
authors.affiliation: Graduate School of Brain Science, Doshisha University, Kyoto, 6190225, Japan mmidorik@mail.doshisha.ac.jp tsakaba@mail.doshisha.ac.jp.
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Midorikawa
authors.affiliation: Graduate School of Brain Science, Doshisha University, Kyoto, 6190225, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Okamoto
authors.affiliation: Graduate School of Brain Science, Doshisha University, Kyoto, 6190225, Japan mmidorik@mail.doshisha.ac.jp tsakaba@mail.doshisha.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakaba
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D015220:Calcium Channels / Q000145:classification / Q000378:metabolism*; D004705:Endocytosis; D005260:Female; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism
chemical_list: D015220:Calcium Channels